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BACKGROUND/AIMS: To establish a consensus in the nomenclature for reporting optical coherence tomography angiography (OCTA findings in uveitis. METHODS: The modified Delphi process consisted of two rounds of electronic questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-one items were included for discussion. The three main areas of discussion were: wide field OCTA (WF-OCTA), nomenclature of OCTA findings and OCTA signal attenuation assessment and measurement. Seventeen specialists in uveitis and retinal imaging were selected by the executive committee to constitute the OCTA nomenclature in Uveitis Delphi Study Group. The study endpoint was defined by the degree of consensus for each question: 'strong consensus' was defined as >90% agreement, 'consensus' as 85%-90% and 'near consensus' as >80% but <85%. RESULTS: There was a strong consensus to apply the term 'wide field' to OCTA images measuring over 70° of field of view, to use the terms 'flow deficit' and 'non-detectable flow signal' to describe abnormal OCTA flow signal secondary to slow flow and to vessels displacement respectively, to use the terms 'loose' and 'dense' to describe the appearance of inflammatory choroidal neovascularisation, and to use the percentage of flow signal decrease to measure OCTA ischaemia with a threshold greater than or equal to 30% as a 'large area'. CONCLUSIONS: This study sets up consensus recommendations for reporting OCTA findings in uveitis by an expert panel, which may prove suitable for use in routine clinical care and clinical trials.
Subject(s)
Tomography, Optical Coherence , Uveitis , Humans , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Uveitis/diagnostic imaging , Retinal Vessels/diagnostic imaging , RetinaABSTRACT
BACKGROUND: We believe that our experience with patients presenting with Coats disease and macular sparing should be shared with our colleagues. We would like to show the effect of posture and prompt intervention in cases with fovea-threatening and/or fovea-involving peripheral Coats disease (FTPCD). This association has been poorly debated in our specialty and literature. We call the attention for the unexpexted scenario of observing the lost of the fovea during some types of traditional and prompt interventional treatments of these cases with previous 20/20 vision (something that we have been studying and observing for many years). In order to publish our best representative cases, we have chosen 8 Brazilian patients (age range, 7-62 years; 5 male) with FTPCD. All patients underwent multimodal imaging and different treatments (observation, sleep-posture repositioning, laser, intraocular steroids, and/or anti-vascular endothelial growth factor therapy). All patients, initially, informed to adopt a sleeping lateral-down position, favoring exudation shifting to the fovea pre-treatment. Most promptly-treated patients in this way (n = 4), developed subretinal fluid and exudates in the macula and some had irreversible central visual loss (n = 3). Patients with recent fovea-involving exudation who changed postural sleep position (to protect the foveal area) before and during treatment fared better, with some preserved central vision and an intact fovea (n = 5). The fundus status was correlated with the gravitational effects of posture before and after treatment. Despite prepared as an observational/interventional study, with a small number of cases, the most difficult part is documenting the sleep position of these patients and its influence in the outcomes as there is not good way to prove how well or poorly the positioning occurred in our cases. Finally, we also intended to call the attention to the fact that Coats disease must be studied in all its clinical stage variants and not only seen as a potential blinding and incurable ocular disease. CASE PRESENTATION: This study is a retrospective and/or interventional analysis of eight cases with a less severe clinical variant of classic Coats disease that we refer to as fovea-threatening and fovea-involving peripheral Coats disease (FTPCD). All cases were unilateral with no systemic disease or family history of Coats disease. The bilateral anterior segment and intraocular pressure were normal in all patients. The characteristics of all patients are shown in the Table. CONCLUSION: The funduscopic features of FTPCD are fundamental to disease understanding and optimal management. Habitual posturing may affect the fundus morphologic features of retinal exudation as observed in all current patients with exudative peripheral Coats disease. When sleep habitual posture is not observed in patients with FTPCD, the effects of prompt invasive treatments can cause rapid visual loss because of foveal subretinal pooling of exudates post-treatment. Initial vigilant adjusting of the habitual sleep posture for several patients with FTPCD, before the indication of traditional invasive treatments (laser and/or pharmacologic medications) can result in improved vision and fundoscopic morphologic features.
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PURPOSE: We investigated the prevalence of ocular abnormalities in infants vertically exposed to Toxoplasma gondii infection during an outbreak in Santa Maria City, Brazil. DESIGN: Consecutive case series. PARTICIPANTS: A total of 187 infants were included. METHODS: The infants were recruited from January 2018 to November 2019. All mothers were screened for syphilis and human immunodeficiency virus before delivery. Toxoplasmosis infection was confirmed in all mothers and infants based on the presence of serum anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. All infants underwent an ophthalmologic examination; ocular abnormalities were documented using a wide-field digital imaging system. Neonatal cranial sonography or head computed tomography was performed in 181 infants, and the cerebrospinal fluid (CSF) was screened for anti-T. gondii IgG and IgM antibodies in 159 infants. Peripheral blood samples from 9 infants and their mothers were analyzed for the presence of T. gondii DNA by real-time polymerase chain reaction. MAIN OUTCOME MEASURES: Ocular abnormalities associated with congenital toxoplasmosis. RESULTS: A total of 187 infants were examined. Twenty-nine infants (15.5%) had congenital toxoplasmosis, of whom 19 (10.2%) had ocular abnormalities, including retinochoroiditis in 29 of 38 eyes (76.3%), optic nerve abnormalities in 5 eyes (13.2%), microphthalmia in 1 eye (2.6%), and cataract in 2 eyes (5.3%). Bilateral retinal choroidal lesions were found in 10 of 19 infants (52.6%). Nine eyes of 6 infants had active lesions, with retinal choroidal cellular infiltrates at the first examination. Thirteen (7.2%) of 181 infants screened presented with cerebral calcifications. Eighty-three percent of the screened infants were positive for anti-T. gondii IgG and negative for IgM antibodies in the CSF. Congenital toxoplasmosis was higher in mothers infected during the third pregnancy trimester, and maternal treatment during pregnancy was not associated with a lower rate of congenital toxoplasmosis. CONCLUSIONS: High prevalence rates of clinical manifestations were observed in infants with congenital toxoplasmosis after a waterborne toxoplasmosis outbreak, the largest yet described. Cerebral calcifications were higher in infants with ocular abnormalities, and maternal infection during the third pregnancy trimester was associated with a higher rate of congenital toxoplasmosis independent of maternal treatment.
Subject(s)
Disease Outbreaks , Toxoplasmosis, Congenital/epidemiology , Toxoplasmosis, Ocular/diagnosis , Toxoplasmosis, Ocular/epidemiology , Antibodies, Protozoan/blood , Antibodies, Protozoan/cerebrospinal fluid , Antiprotozoal Agents/therapeutic use , DNA, Protozoan/genetics , Disease Outbreaks/statistics & numerical data , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/blood , Immunoglobulin M/cerebrospinal fluid , Infant, Newborn , Leucovorin/therapeutic use , Male , Pregnancy , Prevalence , Pyrimethamine/therapeutic use , Real-Time Polymerase Chain Reaction , Retrospective Studies , Sulfadiazine/therapeutic use , Tomography, X-Ray Computed , Toxoplasma/genetics , Toxoplasma/immunology , Toxoplasmosis, Congenital/diagnosis , Toxoplasmosis, Congenital/drug therapy , Toxoplasmosis, Ocular/drug therapy , UltrasonographyABSTRACT
BACKGROUND: Ocular toxoplasmosis is one of the most common causes of intraocular inflammation and posterior uveitis in immunocompetent patients. This paper aims to investigate swept-source optical coherence tomography angiography (SS-OCTA) findings in eyes with active toxoplasmic retinochoroiditis. METHODS: This case series was conducted from November 2017 through October 2019 in two Brazilian centers. 15 eyes of 15 patients with active toxoplasmic retinochoroiditis were included, and were imaged at baseline and after at least 4 weeks of follow-up. All patients underwent ophthalmic examinations and multimodal imaging including SS-OCT and SS-OCTA before and after treatment of ocular toxoplasmosis. The differential diagnoses included toxoplasmosis, syphilis, and human immunodeficiency virus, which were eliminated through serologic and clinical evaluations. RESULTS: All 15 patients presented with positive anti-Toxoplasma gondii immunoglobulin G titers and three also presented with positive anti-T. gondii immunoglobulin M titers. The mean age at examination was 32.4 years ± 12.7 years (range 15-59 years). Sixty percent of the patients were female. In all eyes, the inner retinal layers were abnormally hyperreflective with full-thickness disorganization of the retinal reflective layers at the site of the active toxoplasmic retinochoroiditis. At baseline, 80% of eyes had focal choroidal thickening beneath the retinitis area, and all eyes had a choroidal hyporeflective signal. Before treatment, SS-OCTA showed no OCTA decorrelation signal next to the lesion site in all eyes, and flow signal improvement was noticed after treatment. Three eyes presented with intraretinal vascular abnormalities during follow-up. SS-OCTA showed retinal neovascularization in one patient and a presumed subclinical choroidal neovascular membrane in another patient. CONCLUSIONS: SS-OCT and SS-OCTA are useful for assessing unexpected structural and vascular retinal and choroidal changes in active and post-treatment toxoplasmic retinochoroiditis and these findings are useful for clinical practice.
Subject(s)
Curcumin/administration & dosage , Retina/pathology , Vitreoretinopathy, Proliferative/drug therapy , Vitreous Body/pathology , Animals , Electroretinography , Enzyme Inhibitors/administration & dosage , Intravitreal Injections , Male , Rabbits , Tomography, Optical Coherence/methods , Vitreoretinopathy, Proliferative/diagnosisABSTRACT
Importance: Yellow fever virus (YFV) is a reemerging, potentially lethal arboviral disease that has been occurring recently in Africa and South America. Poor levels of immunization have facilitated the viral spread in southeastern Brazil, leading to an unprecedented outbreak that started in late 2016. Although human cases have been linked to sylvatic mosquitoes, the concern is that YFV may spread to urban centers infested with Aedes aegypti and Aedes albopictus mosquitoes and start a true urban cycle. Objective: To describe the ocular findings in patients with acute YFV infection. Design, Setting, Participants: Two adults with an acute YFV infection in southeastern Brazil underwent an ophthalmologic and ocular ultrasonographic examination in early 2018. Main Outcomes and Measures: Ocular findings in patients with acute YFV infection. Results: Both patients presented with increased choroidal thickness bilaterally seen on ocular ultrasonography. A man in his late 50s who had not been vaccinated previously also presented with bilateral, midperipheral, 360° choroidal detachment and yellowish subretinal lesions. After clinical deterioration and liver transplant, the man died. A woman in her early 30s who had been vaccinated previously for YFV presented with increased retinal venous congestion bilaterally. She was discharged with mild conjunctival chemosis and icterus. Conclusions and Relevance: These reports describe different patterns of ocular findings associated with YFV acute infection. However, the exact mechanism involved in the retinal and choroidal findings remains unclear.
Subject(s)
Choroid/pathology , Retina/pathology , Yellow Fever/pathology , Adult , Animals , Female , Humans , Male , Middle AgedABSTRACT
PURPOSE: To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions. METHODS: This was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated. Patient demographics and ocular details were compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ injections were recorded and defined as either procedure-related or drug-related. RESULTS: A total of 1704 eyes of 1562 patients received 5914 IVZ injections (mean±SD: 3.73±3.94) during a period of 2.5 years. The age of patients was 60.6±12.8 years (mean±SD) and included diverse chorioretinal pathologies. Both ocular (one case of endophthalmitis, three cases of intraocular inflammation, and one case each of conjunctival thinning/necrosis and scleral nodule) and systemic adverse events (two cases of myocardial infarction, one case of stroke and two deaths) were infrequent. CONCLUSION: This constitutes the largest pooled safety report on IVZ use and includes patients from 14 centres distributed across the globe. It shows that IVZ has an acceptable ocular and systemic safety profile with incidences of adverse events similar to those of other vascular endothelial growth factor inhibitory drugs. The analysis supports the continued use of IVZ in various retinal disorders.
Subject(s)
Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retina/pathology , Retinal Diseases/drug therapy , Visual Acuity , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Intravitreal Injections/statistics & numerical data , Male , Middle Aged , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Retinal Diseases/diagnosis , Retrospective Studies , Time Factors , Tomography, Optical Coherence , Treatment OutcomeABSTRACT
PURPOSE: To investigate the binding affinity, stability, and sterility of aflibercept and ziv-aflibercept to vascular endothelial growth factor (Holash et al. in Proc Natl Acad Sci USA 99(17):11393-11398, 2002. 10.1073/pnas.172398299) after compounding and storage for up to 28 days at 4 °C and - 8 °C. METHODS: Tuberculin-type 1-mL syringes were prepared containing aflibercept (40 mg/mL) and ziv-aflibercept (25 mg/mL). Samples were stored at 4 °C and - 8 °C for 0, 14, and 28 days and evaluated for the binding affinity of anti-VEGF to VEGF and stability using enzyme-linked immunosorbent assays. The evaluation of sample sterility was performed. RESULTS: Laboratory trials with aflibercept and ziv-aflibercept showed preservation of the drug-binding capability to recombinant VEGF when stored in plastic syringes for up to 28 days at 4 °C and - 8 °C. No significant decrease in mass or concentration were observed. Microbiologic evaluations did not detect contamination in the syringes. CONCLUSIONS: The current study corroborates that compounded anti-VEGF drugs aflibercept and ziv-aflibercept do not loose stability or binding affinity and do not become contaminated if prepared under sterile conditions and stored at 4 °C or - 8 °C for 14 or 28 days.
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BACKGROUND AND OBJECTIVE: To demonstrate the advantage of optical coherence tomography angiography (OCTA) for the diagnosis and management of proliferative macular telangiectasia type 2 (MacTel2) masquerading as neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: This is an observational cases series. Three patients referred with the diagnosis of neovascular AMD were identified in this retrospective study. In addition to color fundus, fluorescein angiography, and spectral-domain OCT (SD-OCT) imaging, SD-OCTA (AngioPlex; Carl Zeiss Meditec, Dublin, CA) was performed. RESULTS: SD-OCTA revealed bilateral parafoveal retinal microvascular changes in three patients and unambiguously confirmed the diagnosis of MacTel2. CONCLUSION: OCTA is an important tool for the correct diagnosis of MacTel2 in older patients with the concomitant or masquerading diagnosis of AMD. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:303-312.].
Subject(s)
Choroidal Neovascularization/diagnosis , Computed Tomography Angiography , Diagnostic Techniques, Ophthalmological , Macular Degeneration/diagnosis , Retinal Telangiectasis/diagnostic imaging , Tomography, Optical Coherence/methods , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND AND OBJECTIVE: To study the safety and efficacy of intravitreal injections of ziv-aflibercept (IVI-ZA) (Zaltrap; Sanofi-Aventis and Regeneron Pharmaceuticals, Tarrytown, NY) during a period of 48 weeks in patients with diabetic macular edema (DME). PATIENTS AND METHODS: Seven consecutive patients with DME were enrolled and submitted to 12 consecutive IVI-ZA with a 4-week interval. The safety parameters included changes in full-field electroretinogram (ERG) and systemic or ocular complications, and the efficacy parameters were the mean change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: No significant differences were found in any ERG component after IVI-ZA, and no systemic or ocular complication was observed. The improvement of BCVA was most significant after the first IVI-ZA and remained until week 48 (P < .05). The CRT significantly decreased during the course of 48 weeks. CONCLUSION: The 48-week results are consistent with our previous 24-week findings, supporting IVI-ZA as a safe, efficient, and well-tolerated therapy for patients with DME. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:245-250.].
Subject(s)
Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Visual Acuity , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Dose-Response Relationship, Drug , Electroretinography , Female , Follow-Up Studies , Humans , Intravitreal Injections , Macula Lutea/pathology , Macular Edema/diagnosis , Macular Edema/etiology , Male , Middle Aged , Prospective Studies , Time Factors , Tomography, Optical Coherence , Treatment OutcomeABSTRACT
Zika virus (ZIKV) is an arbovirus mainly transmitted to humans by mosquitoes from Aedes genus. Other ways of transmission include the perinatal and sexual routes, blood transfusion, and laboratory exposure. Although the first human cases were registered in 1952 in African countries, outbreaks were only reported since 2007, when entire Pacific islands were affected. In March 2015, the first cases of ZIKV acute infection were notified in Brazil and, to date, 48 countries and territories in the Americas have confirmed local mosquito-borne transmission of ZIKV. Until 2015, ZIKV infection was thought to only cause asymptomatic or mild exanthematous febrile infections. However, after explosive ZIKV outbreaks in Polynesia and Latin American countries, it was confirmed that ZIKV could also lead to Guillain-Barré syndrome and congenital birth abnormalities. These abnormalities, which can include neurologic, ophthalmologic, audiologic, and skeletal findings, are now considered congenital Zika syndrome (CZS). Brain abnormalities in CZS include cerebral calcifications, malformations of cortical development, ventriculomegaly, lissencephaly, hypoplasia of the cerebellum and brainstem. The ocular findings, which are present in up to 70% of infants with CZS, include iris coloboma, lens subluxation, cataract, congenital glaucoma, and especially posterior segment findings. Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were seen in histologic analyses of eyes from deceased fetuses. To date, there is no ZIKV licensed vaccines or antiviral therapies are available for treatment. Preventive measures include individual protection from mosquito bites, control of mosquito populations and the use of barriers measures such as condoms during sexual intercourse or sexual abstinence for couples either at risk or after confirmed infection. A literature review based on studies that analyzed ocular findings in mothers and infants with CZS, with or without microcephaly, was conducted and a theoretical pathophysiologic explanation for ZIKV-ocular abnormalities was formulated.
Subject(s)
Eye Infections, Viral/congenital , Pregnancy Complications, Infectious/virology , Zika Virus Infection/congenital , Zika Virus , Eye Infections, Viral/complications , Eye Infections, Viral/transmission , Female , Humans , Microcephaly/complications , Microcephaly/virology , Pregnancy , Zika Virus/pathogenicity , Zika Virus Infection/complications , Zika Virus Infection/transmissionABSTRACT
BACKGROUND/PURPOSE: To describe the ocular findings of two infants with congenital Zika syndrome born in São Paulo state, Brazil, outside the primary outbreak region. METHODS: Two female infants with congenital Zika syndrome were submitted to a complete screening for infectious diseases, as well as ocular examination, fundus photography, and optical coherence tomography of the retina. One of the infants was submitted to ocular ultrasound. RESULTS: Both children showed positive serology for Zika virus, and other infectious diseases were ruled out. On fundus examination, one newborn had extensive bilateral macular chorioretinal atrophy with hyperpigmented borders associated with gross pigment mottling, as well as atrophic well-limited roundish peripheral lesions in the right eye. Spectral domain optical coherence tomography of the right eye showed complete chorioretinal atrophy in the temporal quadrant. The other infant presented bilateral gross pigment mottling in a paramacular location and a normal optical coherence tomography. DISCUSSION: In this report, the ophthalmologic findings of two infants with Zika syndrome and ocular findings born in São Paulo state, Brazil, are described. Optical coherence tomography findings demonstrate the broad range of retinal damage caused by congenital Zika virus infection. CONCLUSION: The autochthonous cases of infants with congenital Zika syndrome and ocular findings described in this report demonstrate that Zika virus infection is not limited to northeast Brazil, with the potential for even greater spread.
Subject(s)
Eye Infections, Viral/virology , Pregnancy Complications, Infectious/diagnosis , Retinal Diseases/virology , Zika Virus Infection/diagnosis , Female , Humans , Infant , Infant, Newborn , PregnancyABSTRACT
Purpose: We compared area measurements for the same neovascular lesions imaged using swept source optical coherence tomography angiography (SS-OCTA) and enlarging scan patterns. Methods: Patients with neovascular age-related macular degeneration were imaged using a 100-kHz SS-OCTA instrument (PLEX Elite 9000). The scanning protocols included the 3 × 3, 6 × 6, 9 × 9, and 12 × 12 mm fields of view. Two groups were studied. Group 1 included small lesions contained within the 3 \( \times \) 3 mm scan, and Group 2 included larger lesions that were fully contained within the 6 \( \times \) 6 mm scan. Results: A total of 30 eyes of 26 patients were enrolled in Group 1 and 30 eyes of 25 patients were enrolled in Group 2. In Group 1, the automated mean lesion area measurements were 1.11 (SD = 0.78), 1.14 (SD = 0.80), and 1.27 (SD = 0.82) mm2 for the 3 \( \times \) 3, 6 \( \times \) 6, and 12 \( \times \) 12 mm scans, respectively (ANOVA P < 0.001; post hoc comparisons, P = 0.184, 3 \( \times \) 3 vs. 6 \( \times \) 6 mm; P < 0.001 for the other two pairs). In Group 2, the automated mean lesion area measurements were 5.43 (SD = 2.56), 5.53 (SD = 2.48), and 5.49 (SD = 2.65) mm2 for the 6 \( \times \) 6, 9 \( \times \) 9, and 12 \( \times \) 12 mm scans, respectively (ANOVA P = 0.435; post-hoc comparisons, P = 0.062, 6 \( \times \) 6 vs. 9 \( \times \) 9 mm; P = 0.553, 6 \( \times \) 6 vs. 12 \( \times \) 12 mm; P = 0.654, 9 \( \times \) 9 vs. 12 \( \times \) 12 mm). Conclusions: The similarity in lesion area measurements across different scan patterns suggests that SS-OCTA imaging can be used to follow quantitatively the enlargement of choroidal neovascularization as the disease progresses.
Subject(s)
Choroid/blood supply , Choroidal Neovascularization/diagnosis , Ciliary Arteries/pathology , Computed Tomography Angiography , Retinal Vessels/pathology , Tomography, Optical Coherence/methods , Wet Macular Degeneration/diagnosis , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
PURPOSE: To discuss the characteristics, indications and adverse events (AEs) of sustained-release corticosteroid devices for the treatment of cystoid macular edema (CME). RECENT FINDINGS: Ozurdex® is approved for the treatment of diabetic macular edema (DME), retinal vein occlusion related-CME and noninfectious posterior uveitis (NIPU). It releases dexamethasone over a maximum period of 6 months making repeated intravitreal injections necessary for recurrent CME. Iluvien® releases fluocinolone for up to 36 months and is effective for the treatment of chronic DME. Retisert® (Bausch & Lomb, Rochester, NY) also releases fluocinolone, and is approved for chronic NIPU. Both Iluvien® and Retisert® are non-biodegradable devices and are highly associated with cataract and glaucoma. SUMMARY: Long-acting intraocular corticosteroid formulations offer a more predictable drug-release profile and reduced dosing frequency in comparison to conventional formulations of the same compounds but the risk-benefit ratio must be taken into consideration previous to the implantation of those devices.
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PURPOSE: To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. METHODS: Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. RESULTS: Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm to 8.08 ± 1.34 mm, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. CONCLUSION: Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.
Subject(s)
Electroretinography/methods , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retina/physiopathology , Visual Acuity , Wet Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Intravitreal Injections , Male , Middle Aged , Prospective Studies , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Retina/diagnostic imaging , Retina/drug effects , Time Factors , Tomography, Optical Coherence , Treatment Outcome , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/physiopathologyABSTRACT
In the last few years, monoclonal antibodies have revolutionized the treatment of retinal neovascular diseases. More recently, a different class of drugs, fusion proteins, has provided an alternative treatment strategy with pharmacological differences. In addition to commercially available aflibercept, two other drugs, ziv-aflibercept and conbercept, have been studied in antiangiogenic treatment of ocular diseases. In this scenario, a critical review of the currently available data regarding fusion proteins in ophthalmic diseases may be a timely and important contribution. Aflibercept, previously known as VEGF Trap Eye, is a fusion protein of VEGF receptors 1 and 2 and a treatment for several retinal diseases related to angiogenesis. It has firmly joined ranibizumab and bevacizumab as an important therapeutic option in the management of neovascular AMD-, DME- and RVO-associated macular edema. Ziv-aflibercept, a systemic chemotherapeutic agent approved for the treatment of metastatic colorectal cancer, has recently drawn attention because of its potential for intravitreal administration, since it was not associated with ERG-related signs of toxicity in an experimental study and in human case reports. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity for VEGF and a long half-life in vitreous. It has been studied in a phase three clinical trial and has shown efficacy and safety. This review discusses three fusion proteins that have been studied in ophthalmology, aflibercept, ziv-aflibercept and conbercept, with emphasis on their clinical application for the treatment of retinal diseases.
ABSTRACT
IMPORTANCE: Zika virus (ZIKV) can cause severe changes in the retina and choroid that may result in marked visual impairment in infants with congenital Zika syndrome (CZS), the term created for a variety of anomalies associated with intrauterine ZIKV infection. OBJECTIVE: To evaluate the affected retinal layers in infants with CZS and associated retinal abnormalities using optical coherence tomography (OCT). DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, consecutive case series included 8 infants (age range, 3.0-5.1 months) with CZS. Optical coherence tomographic images were obtained in the affected eyes of 7 infants with CZS who had undergone previous ophthalmologic examinations on March 17, 2016, and in 1 infant on January 1, 2016. An IgM antibody-capture enzyme-linked immunosorbent assay for ZIKV was performed on the cerebrospinal fluid samples of 7 of the 8 infants (88%), and other congenital infections were ruled out. MAIN OUTCOMES AND MEASURES: Observation of retinal and choroidal findings in the OCT images. RESULTS: Among the 8 infants included in the study (3 male; 5 female; mean [SD] age at examination, 4.1 [0.7] months), 7 who underwent cerebrospinal fluid analysis for ZIKV had positive findings for IgM antibodies. Eleven of the 16 eyes (69%) of the 8 infants had retinal alterations and OCT imaging was performed in 9 (82%) of them. Optical coherence tomography was also performed in 1 unaffected eye. The main OCT findings in the affected eyes included discontinuation of the ellipsoid zone and hyperreflectivity underlying the retinal pigment epithelium in 9 eyes (100%), retinal thinning in 8 eyes (89%), choroidal thinning in 7 eyes (78%), and colobomatouslike excavation involving the neurosensory retina, retinal pigment epithelium, and choroid in 4 eyes (44%). CONCLUSIONS AND RELEVANCE: Zika virus can cause severe damage to the retina, including the internal and external layers, and the choroid. The colobomatouslike finding seen in the OCT images relate to the excavated chorioretinal scar observed clinically.
Subject(s)
Eye Infections, Viral/diagnosis , Retina/pathology , Retinal Diseases/diagnosis , Tomography, Optical Coherence/methods , Zika Virus Infection/diagnosis , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Eye Infections, Viral/congenital , Eye Infections, Viral/virology , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Infant , Male , Retinal Diseases/congenital , Retrospective Studies , Visual Acuity , Zika Virus/immunology , Zika Virus Infection/congenital , Zika Virus Infection/virologyABSTRACT
Fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been the gold standard for the evaluation of retinal and choroidal vasculature in the last three decades and have revolutionized the diagnosis of retinal and choroidal vascular diseases. The advantage of these imaging modalities lies in their ability to document retinal and choroidal vasculature through the dynamic assessment of contrast transit over time in the intravascular and extravascular spaces. However, disadvantages include the absence of depth resolution, blurring of details by contrast leakage, and the inability to selectively evaluate different levels of the retinal and choroidal microvasculature. In addition, these angiographic methods require intravenous dye, which may cause adverse reactions such as nausea, vomiting, and rarely, anaphylaxis. Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique that, in contrast to dye-based angiography, is faster and depth-resolved, allowing in some cases for more precise evaluation of the vascular plexuses of the retina and choroid. The method has been demonstrated in the assessment of various vascular diseases such as venous occlusions, diabetic retinopathy, macular neovascularization, and others. Limitations of this imaging modality include a small registered field of view and the inability to visualize leakage and dye transit over time. It is also subject to a variety of artifacts, including those generated by blinking and eye movement during image acquisition. However, more than an alternative for FA and ICGA, OCTA is bringing new insights to our understanding of retinal and choroidal vascular structure and is changing fundamental paradigms in the clinical management of pathologic conditions. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:848-861.].