Anti-vascular Endothelial Growth Factor Medications Research Articles

Mapping research trends in diabetic retinopathy from 2010 to 2019

Background:Although many publications in diabetic retinopathy (DR) have been reported, there is no bibliometric analysis.Purpose:To perform a bibliometric analysis in the field of diabetic retinopathy (DR) research, to characterize the current international status of DR research, to identify the most effective factors involved in this field, and to explore research hotspots in DR research.Methods:Based on the Web of Science Core Collection (WoSCC), a bibliometric analysis was conducted to investigate the publication trends in research related to DR. Knowledge maps were constructed by VOSviewer v.1.6.10 to visualize the publications, the distribution of countries, international collaborations, author productivity, source journals, cited references and keywords, and research hotspots in this field.Results:In total, 11,839 peer-reviewed papers were retrieved on DR from 2010 to 2019, and the annual research output increased with time. The United States ranks highest among countries with the most publications. The most active institution is the University of Melbourne. Wong, TY contributed the largest number of publications in this field. Investigative Ophthalmology & Visual Science was the most prolific journal in DR research. The top-cited references mainly investigated the use of anti-vascular endothelial growth factor (VEGF) medications in the management of DR, and the keywords formed 6 clusters:1.pathogenesis of DR;2.epidemiology and risk factors for DR;3.treatments for DR;4.screening of DR;5.histopathology of DR; and6.diagnostic methods for DR.Discussion:With the improvement of living standard, DR has gradually become one of the important causes of blindness, and has become a hot spot of public health research in many countries. The application of deep learning and artificial intelligence in diabetes screening and anti-VEGF medications in the management of DR have been the research hotspots in recent 10 years.Conclusions:Based on data extracted from the WoSCC, this study provides a broad view of the current status and trends in DR research and may provide clinicians and researchers with insight into DR research and valuable information to identify potential collaborators and partner institutions and better predict their dynamic directions.

Intravitreal anti-vascular endothelial growth factor medications during pregnancy: current perspective.

Anti-vascular endothelial growth factor (VEGF) medications are widely used for treatment of a number of vitreoretinal disorders. However, the evidence for their effect on fetal and maternal health during pregnancy is very limited. The goal of this article is to accumulate evidence for the indications of anti-VEGF medications during pregnancy and their effects on maternal and fetal health. Review of literature regarding anti-VEGF administration during pregnancy and using PubMed database without language or date limit. The main indications for treatment with intravitreal anti-VEGF medications include choroidal neovascularization (CNV) followed by retinal vascular occlusion (RVO) and complications of diabetes such as neovascular glaucoma, diabetic retinopathy (DR) and diabetic macular edema (DME). Among anti-VEGF medications, only ranibizumab and bevacizumab have been used during pregnancy with latter by far more than the former. Women of childbearing age should be consulted regarding the potential adverse effects of anti-VEGF medications on fetal health and the risk of early pregnancy loss. They should be strongly encouraged to use appropriate contraceptive methods during treatment. A timely obstetrics consultation may help in this situation. Attempt for pregnancy should be withheld for at least 3months following last injection of ranibizumab and aflibercept, and for at least 6months following last injection of bevacizumab.

Cost-minimization Analysis of Ranibizumab versus Aflibercept in the Treatment of Neovascular Age-related Macular Degeneration in Colombia

ABSTRACT Background In 2020 Colombia may expect to have close to 231,700 patients with neovascular age-related macular degeneration (ARMD). Treatment of neovascular ARMD involves the sequential Intra-vitreal injections of anti-vascular endothelial growth factor (anti-VEGF therapy) medications. The efficacy and safety of anti-VEGF therapy on a treat-and-extend (T&E) dosing scheme are similar when ranibizumab or aflibercept are administered. Objective : A cost-minimization analysis from the payer`s perspective in Colombia projects treatment expenses of anti-VEGF therapy using aflibercept or ranibizumab on T&E regimens for the treatment of neovascular ARMD. Methods : A model projects the expenses of the compared treatment regimens for two and five-year periods beginning on February 2020. The model used information from clinical trials, case series and meta-analyses on the compared treatment regimens, demographic, epidemiologic and economic data originated from the Colombian government sources. A 3% discount rate was applied. Results : Projected cost differences in favor of ranibizumab after two and five-year treatment periods beginning February 2020 could be close to U.S. $ 4,861 and U.S $ 7,241 per treated eye, respectively. If all patients with unilateral and bilateral neovascular ARMD in Colombia were to receive appropriate anti-VEGF therapy for two years, the projected expected cost difference in favor of ranibizumab could be close to U.S. $ 462,717,092 dollars. Conclusion : Within the Colombian healthcare setting anti-VEGF therapy on a T&E regimen utilizing ranibizumab for neovascular ARMD may be cost-saving compared with employing aflibercept. Despite cost favorability, ranibizumab should not be the only therapeutic option since in clinical practice alternatives are required.

Anti–Vascular Endothelial Growth Factor and Panretinal Photocoagulation Use after Protocol S for Proliferative Diabetic Retinopathy

To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the Diabetic Retinopathy Clinical Research Network protocol S. A retrospective, cross-sectional study from January 2012, through September 2019, using a nationally representative claims-based database, Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF agents. Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 2015). Annual rates of anti-VEGF or PRP treatments per 1000 treated eyes with PDR. From 2012 through 2019, 10 035 PRP or anti-VEGF treatments were administered to 3685 PDR eyes. Of these, 63.6% (n= 6379) were anti-VEGF agents, and 36.4% (n= 3656) were PRP treatments. Throughout treatment, 88.7% of eyes treated with anti-VEGF received the same agent and 7.7% were treated with both PRP and anti-VEGF agents. Panretinal photocoagulation rates declined from 784/1000 treated eyes in 2012 to 566/1000 in 2019 (pre-Protocol S: β= -32 vs. post-Protocol S: -77; P= 0.005), whereas anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (β= -48 vs. 161, respectively; P= 0.001). Panretinal photocoagulation rates in diabetic macular edema (DME) eyes did not significantly differ from 474/1000 in 2012 to 363/1000 in 2019 (β= -9 vs. -58 respectively; P= 0.091), and anti-VEGF rates increased from 1533/1000 in 2012 to 2096/1000 in 2019 (β= -57 vs. 187; P= 0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (β= -31 vs. -111, respectively; P < 0.001), and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (β= -48 vs. 140, respectively; P < 0.001). Following the publication of Protocol S, PRP rates decreased, while anti-VEGF rates increased. Panretinal photocoagulation rates did not significantly change among eyes with DME. Our findings indicate the impact that randomized controlled trials can have on real-world practice patterns.

Update on Anti-Vascular Endothelial Growth Factor Safety for Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a neovascular retinal disorder that occurs in infants born prematurely. Nowadays, ROP constitutes a leading cause of childhood blindness worldwide and for decades the standard of care has involved peripheral retinal ablation. However, this type of treatment requires the use of specialized equipment by well-trained physicians, has been associated with poor structural and visual outcomes in some preterm infants, and despite its adequate application, some cases of ROP may continue to progress. Therefore, the need for simpler and more efficient strategies made anti-vascular endothelial growth factor (anti-VEGF) medications an appealing option for treatment. Recently, the use of anti-VEGF agents for ROP has increased worldwide; nevertheless, this practice remains off-label, and there is a lack of information regarding its safety profile and the possibility of unfavorable long-term outcomes causes the utmost concern. This review updates the recent evidence regarding the systemic and ocular safety of anti-VEGF treatment for ROP.

Efficacy of Aflibercept Treatment and Its Effect on the Retinal Perfusion in the Oxygen-Induced Retinopathy Mouse Model of Retinopathy of Prematurity

Introduction: Bevacizumab and ranibizumab, which are anti-vascular endothelial growth factor (VEGF) medications, are used frequently in the treatment for retinopathy of prematurity (ROP) in infants. Aflibercept, or VEGF Trap, has been used anecdotally, but translation and clinical studies are lacking. Objective: This study investigates the efficacy of aflibercept at reducing areas of non-perfused retina and studies its effect on normal angiogenesis in the oxygen-induced retinopathy mouse model of ROP. Methods: C57BL/6 J mice were assigned to room air control (n = 21 eyes) or hyperoxia with 75% oxygen (n = 84 eyes). The hyperoxic mice were assigned to 1 of 3 groups: 0 ng (n = 14 eyes), 100 ng (n = 35 eyes), or 1,000 ng (n = 35 eyes) of intravitreal aflibercept administered on postnatal day 14. Eyes were enucleated at PN17 and PN25 postinjection. Retinas were stained with anti-collagen IV antibody and photographed with microscopy. Areas of perfused and non-perfused retina were quantified using ImageJ software. Statistical comparisons were made using ANOVA with Tukey post hoc comparisons. Results: At PN17, there was no significant difference in the area of non-perfused retina between the hyperoxic control and the 100 and 1,000 ng aflibercept groups. At PN25, the 100 ng (p < 0.05) and 1,000 ng (p = 0.008) treatment groups displayed less non-perfusion compared to hyperoxic controls. At the 1,000 ng dose, there was increased non-perfusion compared to the 100 ng dose (p = 0.02). There was reduced non-perfusion by PN25 compared to PN17 for the 100 ng group (p < 0.05), with no difference in the 1,000 ng group. Conclusions: The study shows that the area of non-perfused retina decreases effectively with aflibercept at PN25 with 100 ng dosage. With the 1,000 ng dosage, there is an inhibition of the physiologic angiogenesis with a higher area of non-perfused retina.

PSS3 COST-MINIMIZATION ANALYSIS OF RANIBIZUMAB VERSUS AFLIBERCEPT IN THE TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN COLOMBIA

Colombia expects to have close to 234,200 patients with neovascular ARMD by the year 2020. Treatment of neovascular ARMD involves the sequential Intra-vitreal injections of anti-vascular endothelial growth factor medications (anti-VEGF therapy). The efficacy and safety of anti-VEGF therapy on a treat-and-extend (TAE) dosing scheme are similar when ranibizumab or aflibercept are administered. This cost-minimization analysis from the payer`s perspective in Colombia projects treatment expenses of anti-VEGF therapy using aflibercept or ranibizumab on TAE regimens for the treatment of neovascular ARMD. A model projects the expenses of the compared treatment regimens for the period between years 2020 and 2025. The model considered medication and treatment costs, information from clinical trials and meta-analyses on the compared treatment regimens, local demographic, epidemiologic and economic data. In the treatment of neovascular ARMD in Colombia, for a five-year period beginning 2020 and using TAE dosing regimens, anti-VEGF therapy using ranibizumab may be cost saving when compared with therapy using aflibercept. Savings in the five-year period could be close to U.S. $ 6,917 per patient. If all patients with neovascular ARMD in Colombia receive anti-VEGF therapy between the years 2020 and 2025, the minimal expected savings for the Colombian health care system with the use of ranibizumab as compared to aflibercept could be close to U.S. $ 497,249,492. In the Colombian health care setting and for a five-year projection beginning 2020, anti-VEGF therapy on a TAE regimen utilizing ranibizumab for neovascular ARMD may be cost saving compared with the administration of aflibercept.

Anti-vascular endothelial growth factor for neovascular glaucoma.

Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reportedthe effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG. To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more type of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 22 March 2019; metaRegister of Controlled Trials to 13 August 2013; and two additional trial registers to 22 March 2019. We did not use any date or language restrictions in the electronic search for trials. We included randomised controlled trials (RCTs) of people treated with anti-VEGF medications for NVG. Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion. We included four RCTs (263 participants) and identified one ongoing RCT. Each trial was conducted in a different country: China, Brazil, Egypt, and Japan. We assessed the trials to have an unclear risk of bias for most domains due to insufficient information. Two trials compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP. We did not combine these two trials due to substantial clinical and statistical heterogeneity. One trial randomised participants to receive an injection of either an intravitreal anti-VEGF medication or placebo at the first visit, followed by non-randomised treatment according to clinical findings after one week. The last trial randomised participants to PRP with and without ranibizumab, but details of the study were unavailable for further analysis. Two trials that examined IOP showed inconsistent results. One found inconclusive results for mean IOP between participants who received anti-VEGF medications and those who did not, at one month (mean difference [MD] -1.60 mmHg, 95% confidence interval [CI] -4.98 to 1.78; 40 participants), and at one year (MD 1.40 mmHg, 95% CI -4.04 to 6.84; 30 participants). Sixty-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 60% without anti-VEGF medications. In another trial, those who received anti-VEGF medications were more likely to reduce their IOP than those who did not receive them, at one month (MD -6.50 mmHg, 95% CI -7.93 to -5.07; 40 participants), and at one year (MD -12.00 mmHg, 95% CI -16.79 to -7.21; 40 participants). Ninety-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 50% without anti-VEGF medications. The certainty of a body of evidence was low for this outcome due to limitations in the design and inconsistency of results between studies. Post-operative complications included anterior chamber bleeding (3 eyes) and conjunctival hemorrhage (2 participants) in the anti-VEGF medications group, and retinal detachment and phthisis bulbi (1 participant each) in the control group. The certainty of evidence is low due to imprecision of results and indirectness of evidence. No trial reported the proportion of participants with improvement in visual acuity, proportion of participants with complete regression of new iris vessels, or the proportion of participants with relief of pain and resolution of redness at four- to six-week, or one-year follow-up. Currently available evidence is uncertain regarding the long-term effectiveness of anti-VEGF medications, such as intravitreal ranibizumab or bevacizumab or aflibercept, as an adjunct to conventional treatment in lowering IOP in NVG. More research is needed to investigate the long-term effect of these medications compared with, or in addition to, conventional surgical or medical treatment in lowering IOP in NVG.

Gender-related differences in patients treated with intravitreal anti-vascular endothelial growth factor medication for diabetic macular oedema.

Diabetes prevalence is constantly rising, involving the eyes with damage including development of diabetic macular oedema. Since 2012, intravitreal anti-vascular endothelial growth factor medication is available for diabetic macular oedema treatment. Endocrinological studies have shown that fewer women are affected by diabetes. However, when affected, they exhibit more severe diabetic complications than men. We have investigated gender-related differences in diabetic macular oedema and outcome in an ophthalmological tertiary referral hospital. We included 88 patients (54 males and 34 females) with 112 eyes (68 male and 44 female) having clinically significant diabetic macular oedema, treated with anti-vascular endothelial growth factor medication. A 1 year follow-up was performed in all patients (visual acuity and optical coherence tomography). Previous retinal surgery was an exclusion criterion, as were other retinal pathologies. The mean visual acuity and mean central retinal thickness at baseline were 0.53 logMAR (male 0.49 and female 0.595) and 469 μm (male 452 μm and female: 494 μm), respectively. After 360 days, mean visual acuity changed by -0.07 (±0.36) logMAR (male -0.11 and female +0.01) and mean central retinal thickness changed by -119 μm (male -113 μm and female -127 μm). For visual acuity, a significant difference was noted at baseline (p = 0.02) and at 1 year (p < 0.001). Males received 5.6 injections and females received 5.68 injections in 1 year. Our study showed that female patients with diabetic macular oedema were diagnosed with and treated for diabetic macular oedema at a stage when visual acuity and optical coherence tomography were worse than those in their male counterparts. This gender difference could not be reduced, despite similar numbers of injections. Female diabetic patients should therefore be assessed early for ophthalmological pathologies.

EFFECT OF SERIAL ANTERIOR CHAMBER PARACENTESIS ON SUSTAINED INTRAOCULAR PRESSURE ELEVATION IN PATIENTS RECEIVING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

To investigate the effect of serial anterior chamber (AC) paracenteses in eyes with sustained elevations of intraocular pressure (IOP) in the setting of repeated intravitreal injections (IVI) of anti-vascular endothelial growth factor medications. This is a retrospective records review of patients undergoing IVI of anti-vascular endothelial growth factor medication (bevacizumab, ranubizumab, or aflibercept), who demonstrated a sustained elevation of preinjection IOP and also received AC paracentesis immediately after IVI on at least three consecutive visits. Changes in preinjection IOP and cup-to-disk (C:D) ratio were compared before and after the initiation of IVI and before and after the introduction of AC paracenteses with each subsequent IVI. Twenty-three eyes of 17 patients receiving a median of 26 IVI experienced a rise in preinjection IOP from 16.3 mmHg to 21.1 mmHg (P = 0.004) and an increase in mean C:D ratio from 0.37 to 0.47 (P = 0.0002). After introduction of AC paracenteses (median of 12), mean IOP was returned to baseline 16.00 mmHg (P = 0.002), mean C:D ratio stabilized (0.50, P = 0.197), and maximum IOP decreased from 26.8 mmHg to 23.0 mmHg (P = 0.05). Nineteen (82.6%) eyes required an increase in topical glaucoma medications during the study period, and 13 (56.5%) still required additional therapies after initiation of AC paracenteses. Five eyes (38.5%) required laser or glaucoma drainage device procedures. Serial AC paracenteses reduced immediate postinjection IOP, and along with standard glaucoma care in most patients, reversed preinjection IOP elevation, and stabilized optic nerve changes associated with repeated intravitreal anti-vascular endothelial growth factor injections in a subset of patients with sustained elevation of preinjection IOP.

Surgical Innovations in the Treatment of Diabetic Macular Edema and Diabetic Retinopathy.

Diabetic macular edema (DME) and complications of proliferative diabetic retinopathy (PDR) are the primary causes of vision loss in patients with diabetic retinopathy. As the incidence of diabetes increases worldwide, new, cost-effective treatments for DME and PDR will become paramount. Currently, anti-vascular endothelial growth factor (anti-VEGF) medications are considered first-line treatment. However, multiple visits for injections and the economic and time burden they entail make this treatment modality less than ideal. Early vitrectomy as well as depot delivery systems for medications could potentially reduce the treatment burden of patients with diabetes, prevent visual loss, and provide long-term stabilization of retinopathy in patients with diabetes. Newer port delivery systems for anti-VEGF medications could oneday make this treatment modality better suited for patients across the globe. Real-world data shows poor compliance with treatment among patients with diabetes. Recent publications show catastrophic results when anti-VEGF treatments are stopped abruptly. The port delivery system for ranibizumab shows maintenance of adequate anti-VEGF levels in the vitreous cavity for many months. Early vitrectomy can provide cost-effective long-term stabilization in eyes with diabetic retinopathy. Microincisional vitrectomy as a treatment for DME and PDR remains controversial and larger trials are needed to definitively prove its superiority over other modalities; however, small-scale data point towards its usefulness in specific populations. Newer port delivery systems of anti-VEGF show promise in decreasing the number of office visits in patients with diabetic retinopathy.

NEW PROPOSAL FOR THE PATHOPHYSIOLOGY OF TYPE 3 NEOVASCULARIZATION AS BASED ON MULTIMODAL IMAGING FINDINGS.

To investigate the imaging characteristics of early Type 3 neovascularization and propose a new pathophysiologic sequence for early disease. Patients were evaluated with a comprehensive ophthalmologic examination to include fundus photography, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, and volume-rendered optical coherence tomography angiography. Relevant literature was also reviewed. There were 10 eyes of 9 patients who had a mean age of 87 (range 79-93) years and 7 were women. The patients were seen to have distributed areas of cystoid macular edema, not necessarily contiguous with areas of fluorescein or optical coherence tomography angiographic evidence of neovascularization, which colocalized with each other. Areas of hemorrhage were not necessarily contiguous with observed neovascularization. In some patients, massive amounts of edema were imaged, although the associated neovascular invasion was small and did not reach deeper portions of the retina. These findings were readily responsive to intravitreal injections of anti-vascular endothelial growth factor (VEGF) medication. Review of published literature showed conflicting pathophysiologic proposals, which did not abide with contemporaneous imaging findings. Type 3 neovascularization likely grows in response to increased cytokine levels, particularly VEGF, in a permissive environment. Elevated levels of VEGF have been shown to cause hemorrhage, edema, and telangiectasis in the macula, suggesting some of the manifestations of Type 3 neovascularization are related to increased tissue VEGF levels and not necessarily to the neovascularization alone. A proposal based on imaging and histopathologic findings and known physiologic effects of VEGF is presented.

Evaluation of a Remote Telemedicine Screening System for Severe Retinopathy of Prematurity.

To evaluate the validity of remote telemedicine screening for retinopathy of prematurity (ROP) in a population of at-risk preterm infants in Iowa and South Dakota. The medical records for all preterm infants screened for ROP at neonatal intensive care units (NICUs) in Sioux City, Iowa, and Sioux Falls, South Dakota, from September 1, 2017, to July 31, 2018, were retrospectively reviewed. The RetCam Shuttle (Natus Medical Inc., Pleasanton, CA) was used to capture retinal images, which were posted on a secure server for evaluation by a pediatric ophthalmologist. Infants with suspected ROP approaching the criteria for treatment with anti-vascular endothelial growth factor (VEGF) medications were transferred to the Children's Hospital and Medical Center NICU in Omaha, Nebraska, where a comprehensive examination was performed and treatment was administered when indicated. The remaining infants received an outpatient comprehensive examination by one of two pediatric ophthalmologists within 2 weeks of discharge. A total of 124 telemedicine examinations were performed on 35 infants during the study period. Remote telemedicine screening for referral-warranted ROP using the RetCam Shuttle had a sensitivity of 100%, specificity of 97%, positive predictive value of 66.7%, and negative predictive value of 100%. Of the three infants transferred for referral-warranted ROP, two required treatment with anti-VEGF medications. Good outcomes were noted in all cases, and no patients progressed beyond stage 3 ROP. Telemedicine screening reliably detected referral-warranted ROP in at-risk premature infants at two remote sites, with no poor outcomes during the 11-month period. These results demonstrate the validity and utility of remote telemedicine screening for ROP. [J Pediatr Ophthalmol Strabismus. 2019;56(3):157-161.].

Rhegmatogenous Retinal Detachment after Intravitreal Injection of Anti–Vascular Endothelial Growth Factor

To report the rate, risk factors, and outcomes of rhegmatogenous retinal detachment (RRD) after intravitreal injection of anti-vascular endothelial growth factor medications. Single-center, retrospective, consecutive review. All patients receiving ranibizumab, bevacizumab, or aflibercept for neovascular age-related macular degeneration or retinal vein occlusion between October 1, 2014, and October 1,2017. The total number of eyes and injections were determined from billing codes. Rhegmatogenous retinal detachment patients were determined from billing records and confirmed with chart review. Rate of retinal detachment and visual acuity outcomes. A total of 180 671 intravitreal injections in 12 718 unique patients were included. An RRD occurred in 24 patients within 3 months after injection, giving a rate of 1 RRD per 7532 intravitreal injections (0.013%) and 1 RRD per 530 patients (0.19%). No association was found between RRD risk after injection and diagnosis (P=0.54), physician experience (P= 0.23), injection site (P= 0.41), caliper use (P= 0.75), or 31- versus 30-gauge needle use (P= 0.18). A retinal tear was found located in the quadrant of the injection site (within 1.5 clock hours of the injection) in 15 of 24 patients (62.5%; P < 0.0001). At the time of RRD diagnosis, the macula was attached in 9 patients (37.5%). Interventions for RRD repair included pars plana vitrectomy (PPV; 15 patients), combined scleral buckle and PPV (4 patients), pneumatic retinopexy (3 patients), and laser or cryotherapy alone (2 patients). Single-surgery success rate was 54.2%, with 54.5% of recurrent detachments caused by proliferative vitreoretinopathy. Average loss from visual acuity recorded at the visit before diagnosis of RRD was 1.0 line for macula-on detachments versus 6.8 lines for macula-off detachments (P= 0.027) at final follow-up (average, 16.3 months). Retinal detachment after intravitreal injection is uncommon, with a rate of approximately 1in7500 injections. Macular status at the time of RRD diagnosis significantly affects visual outcomes.

Prefilled syringes for intravitreal drug delivery.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications play an increasingly critical role in numerous retinal vascular diseases. Initially, anti-VEGF medications came in vials that had to be drawn up by the physician into a syringe for administration. In 2018, the US Food and Drug Administration (US FDA) approved the ranibizumab 0.3 mg prefilled syringe (PFS), and in October 2016, the US FDA approved the ranibizumab 0.5 mg PFS. This article discusses the advantages of the PFS, including reduced injection time, possible reduced risk of endophthalmitis, reduction in intraocular air bubbles and silicone oil droplets, and improved precision in the volume and dose of intravitreal ranibizumab administered, along with possible disadvantages. Implications of the innovation of the PFS on intravitreal injection technique and clinical practice pattern are discussed and reviewed.

Current Practice Preferences and Safety Protocols for Intravitreal Injection of Anti–Vascular Endothelial Growth Factor Agents

To assess current practice preferences and safety measures used for intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) medications and to assess the variability of practice patterns between academic and nonacademic and between early- and later-career ophthalmologists. Cross-sectional survey. Practicing retina specialists who administer intravitreal anti-VEGF injections from the membership pool of the American Society of Retina Specialists. Participants were contacted by e-mail to participate in an anonymous 31-question survey on a common online platform, SurveyMonkey. Preferred practices for various aspects of administering IVIs and adherence to the most recently published guidelines on IVI techniques. Preinjection antibiotic drops were used always or often by 10.9% (43/396) of participants. Antibiotics after injection were used always or often by 16.6% (66/398) of participants. Longer (>15 years) compared with shorter (0-15 years) duration of practice was associated with always or often instilling preinjection antibiotics (13.7% vs. 6.7%; P= 0.028), scrubbing eyelids or lashes with antiseptic (43.6% vs. 30.5%; P= 0.008), and being less likely to instill antiseptic immediately before injection (89.7% vs. 95.7%; P= 0.029). Practicing for more than 25 years was associated with always or often instilling antibiotics after injection (22.5% vs. 13.3%; P= 0.017). Academic compared with nonacademic providers were more likely to wear a cap (16.3% vs. 6.8%; P= 0.006), mask (43.0% vs. 29.9%; P= 0.022), and gloves (64.0% vs. 52.1%; P= 0.050) and to drape the patient (17.4% vs. 9.1%; P= 0.027). Techniques for IVIs vary widely. Use of periprocedure antibiotics has declined, consistent with new evidence demonstrating lack of efficacy in endophthalmitis prevention as well as their potential harm. However, later-career physicians were more likely to continue to use antibiotics and other techniques advised against in the most recent recommendations of expert consensus groups in the United States and Europe. Academic practitioners were more likely to use protective wear during the procedure.

Fluorescein Angiography in Retinopathy of Prematurity: Comparison of Infants Treated with Bevacizumab to Those with Spontaneous Regression

Medium- and long-term sequelae of intravitreal bevacizumab (IVB) for type 1 retinopathy of prematurity (ROP) are uncertain. Our aim was to describe the fluorescein angiography (FA) findings in patients who received IVB as primary treatment for type 1 ROP and compare them to findings in patients with ROP that spontaneously regressed. Retrospective cohort. Twenty-eight patients with a history of ROP who underwent fluorescein angiography between December 1, 2013, and July 31, 2018. Patients were divided into 2 groups based on whether they had received IVB or had ROP that spontaneously regressed. We reviewed the angiograms in the 2 groups for neovascularization (NV) and other abnormal vascular patterns in both the periphery and the posterior pole. Fluorescein angiography findings, including NV, peripheral, and macular vascular abnormalities. Forty eyes of 20 infants were included in the IVB group and 16 eyes of 8 infants in the untreated group. Median gestational age at birth was similar in the 2 groups (24.5 and 24.7 weeks, respectively; P= 0.44), as was the median birth weight (648.5 and 560.0 g, respectively; P= 0.26). Median postmenstrual age at the time of FA was 65.1 and 83.9 weeks, respectively (P= 0.0002). Review of angiograms demonstrated NV in 30.0% and 37.5% in the IVB and untreated cohorts, respectively (P= 0.75). Abnormal vascular patterns in the periphery were similar in both groups (100.0%), whereas posterior pole findings of vessels encroaching onto the fovea were more prevalent in the IVB cohort (65.0% vs. 25.0%; P= 0.009). Fluorescein angiography after bevacizumab for ROP reveals abnormal vascular patterns in all eyes and NV in approximately one-third. Similar abnormal vascular patterns on FA are seen at a similar prevalence after spontaneous regression of ROP. These findings suggest that the abnormal vascular patterns identified by FA in patients with ROP result from the disease process itself rather than as a result of exposure to anti-vascular endothelial growth factor medications.

Fully automated detection of retinal disorders by image-based deep learning.

With the aging population and the global diabetes epidemic, the prevalence of age-related macular degeneration (AMD) and diabetic macular edema (DME) diseases which are the leading causes of blindness is further increasing. Intravitreal injections with anti-vascular endothelial growth factor (anti-VEGF) medications are the standard of care for their indications. Optical coherence tomography (OCT), as a noninvasive imaging modality, plays a major part in guiding the administration of anti-VEGF therapy by providing detailed cross-sectional scans of the retina pathology. Fully automating OCT image detection can significantly decrease the tedious clinician labor and obtain a faithful pre-diagnosis from the analysis of the structural elements of the retina. Thereby, we explore the use of deep transfer learning method based on the visual geometry group 16 (VGG-16) network for classifying AMD and DME in OCT images accurately and automatically. A total of 207,130 retinal OCT images between 2013 and 2017 were selected from retrospective cohorts of 5319 adult patients from the Shiley Eye Institute of the University of California San Diego, the California Retinal Research Foundation, Medical Center Ophthalmology Associates, the Shanghai First People's Hospital, and the Beijing Tongren Eye Center, with 109,312 images (37,456 with choroidal neovascularization, 11,599 with diabetic macular edema, 8867 with drusen, and 51,390 normal) for the experiment. After images preprocessing, 1000 images (250 images from each category) from 633 patients were selected as validation dataset while the rest images from another 4686 patients were used as training dataset. We used deep transfer learning method to fine-tune the VGG-16 network pre-trained on the ImageNet dataset, and evaluated its performance on the validation dataset. Then, prediction accuracy, sensitivity, specificity, and receiver-operating characteristic (ROC) were calculated. Experimental results proved that the proposed approach had manifested superior performance in retinal OCT images detection, which achieved a prediction accuracy of 98.6%, with a sensitivity of 97.8%, a specificity of 99.4%, and introduced an area under the ROC curve of 100%. Deep transfer learning method based on the VGG-16 network shows significant effectiveness on classification of retinal OCT images with a relatively small dataset, which can provide assistant support for medical decision-making. Moreover, the performance of the proposed approach is comparable to that of human experts with significant clinical experience. Thereby, it will find promising applications in an automatic diagnosis and classification of common retinal diseases.

Intravitreal Bevacizumab in Diabetic Retinopathy. Recommendations from the Pan-American Collaborative Retina Study Group (PACORES): The 2016 Knobloch Lecture.

The advent of intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications has revolutionized the treatment of diabetic eye diseases. Herein, we report the outcomes of clinical studies carried out by the Pan-American Collaborative Retina Study Group (PACORES), with a specific focus on the efficacy of intravitreal bevacizumab in the management of diabetic macular edema and proliferative diabetic retinopathy. We will also discuss the use of intravitreal bevacizumab as a preoperative, adjuvant therapy before vitrectomy for proliferative diabetic retinopathy.

VISUAL ACUITY IMPROVEMENT WHEN SWITCHING FROM RANIBIZUMAB TO AFLIBERCEPT IS NOT SUSTAINED.

To assess whether visual benefits exist in switching to aflibercept in patients who have been chronically treated with ranibizumab for neovascular age-related macular degeneration. A multicenter, national, electronic medical record database study was performed. Patients undergoing six continuous monthly ranibizumab injections and then switched to continuous aflibercept were matched to those on continuous ranibizumab therapy. Matching was performed in a 2:1 ratio and based on visual acuity 6 months before and at the time of the switch, and the number of previous ranibizumab injections. Patients who were switched to aflibercept demonstrated transiently significant improvement in visual acuity that peaked at an increase of 0.9 Early Treatment Diabetic Retinopathy Study letters 3 months after the switch, whereas control patients continued on ranibizumab treatment showed a steady decline in visual acuity. Visual acuity differences between the groups were significant (P < 0.05) at 2, 3, and 5 months after the switch. Beginning at 4 months after the switch, the switch group showed a visual acuity decline similar to the control group. Transient, nonsustained improvement in visual acuity occurs when switching between anti-vascular endothelial growth factor agents, which may have implications in treating patients on chronic maintenance therapy on one anti-vascular endothelial growth factor medication.