Simultaneous cytomegalovirus uveitis and HIV retinopathy / Uveíte por citomegalovírus e retinopatia por HIV simultâneas

ABSTRACT A 41 year-old man presented with unilateral vision loss for a week and constitutional symptoms for 3 months. Ophthalmic evaluation revealed cotton wool spots on the right eye and widespread retinal necrosis and hemorrhage on the left eye, suggestive of cytomegalovirus uveitis and HIV infection and retinopathy, and confirmed by serology. The patient was treated with ganciclovir and highly active antiretroviral therapy and preserved contralateral vision. Clinicians should be aware of uveitis and retinopathies to prevent irreversible vision loss and systemic conditions.

RESUMO Paciente do sexo masculino, 41 anos, com queixa de perda de acuidade visual unilateral por 1 semana e sintomas constitucionais por 3 meses. Ao exame oftalmológico, apresentava exsudatos algodonosos, em olho direito, e áreas de necrose e hemorragias retinianas, em olho esquerdo, com suspeita de uveíte por citomegalovírus e retinopatia por HIV, confirmadas por sorologias. O paciente foi tratado com ganciclovir e terapia antirretroviral e preservou a visão contralateral. Os oftalmologistas devem estar atentos para casos de uveítes e retinopatias, para prevenirem perda visual irreversível e condições sistêmicas.

New findings useful for clinical practice using swept-source optical coherence tomography angiography in the follow-up of active ocular toxoplasmosis.

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.

Safety of 5914 intravitreal ziv-aflibercept injections.

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.

Evaluation of aflibercept and ziv-aflibercept binding affinity to vascular endothelial growth factor, stability and sterility after compounding.

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.

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes.

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.].

En-Face Optical Coherence Tomography of Acute Syphilitic Posterior Placoid Chorioretinopathy.

PURPOSE: To report a unique case series of acute syphilitic posterior placoid chorioretinopathy (ASPPC) correlating en-face optical coherence tomography (OCT) with standard imaging modalities. METHODS: In this retrospective case series, multimodal imaging was performed in three ASPPC patients at the time of disease presentation. RESULTS: Clinical and laboratory findings were consistent with the diagnosis of ASPPC. In all the study patients, multiple hyperreflective dot-like lesions distributed in the macular area and observed with en-face OCT at the level of retinal pigment epithelium (RPE) corresponded to the nodular RPE elevations on cross-sectional OCT and to the hyperautofluorescent spots on fundus autofluorescence. In addition, the cross-sectional OCT scans showed disorganization of the outer retinal bands and punctate choroidal hyperreflectivity. CONCLUSION: By combining en-face OCT with multimodal imaging analysis, we propose that a primary inflammation at the level of the choroid may be the pathogenic mechanism for the occurrence of outer retinal band abnormalities.

Cat Scratch Disease: Not a Benign Condition.

PURPOSE: Describe a case series of ocular Cat-scratch-disease (CSD) with vision-threatening findings and poor outcomes, indicating severity of disease. METHODS: Retrospective case series from the Uveitis Department of São Paulo Federal University from 2011 to 2015. RESULTS: In this period, six eyes of four patients had confirmed diagnosis of CSD. Two were male and two female. Mean age was 24.8 years old [7-45]. Two had bilateral disease. Visual acuity at presentation ranged from no light perception to 20/25. Three patients were treated with doxycycline and one with clarithromycin and prednisone. Visual outcome after treatment ranged from counting fingers to 20/20: 5/6 eyes had final visual acuity of less than 20/40 and 3/6 had final visual acuity equal or less than 20/400. CONCLUSION: Although usually described as a benign disease with spontaneous resolution, CSD can present with atypical manifestations such as vascular angiomatous lesions, serous retinal detachment, and vascular occlusion syndromes, carrying a severe course and guarded prognosis.

Arboviruses and the eye.

Arthropod-borne viruses, or arboviruses, are viruses that are transmitted through the bites of mosquitoes and ticks. There are numerous arboviruses throughout the world capable of causing human disease spanning different viral families and genera. Recently, dengue, chikungunya, and zika viruses have emerged as increasingly important arboviruses that can cause human disease, however no specific treatment or vaccine is available for them. In addition, ocular manifestations of these diseases have become more prevalent over the past few years. This review highlights the current understanding on the pathogenesis, systemic changes and ocular findings, emphasizing the retinal manifestations related to dengue, chikungunya, and zika viruses.

Multimodal imaging analyses of hyperreflective dot-like lesions in acute syphilitic posterior placoid chorioretinopathy.

BACKGROUND: Retrospective review of one acute syphilitic posterior placoid chorioretinitis (ASPPC) case with serological evidence of syphilis who had ocular signs and symptoms not attributable to other diseases. Enface and spectral-domain optical coherence tomographySD-OCT were analyzed at the time of presentation and at 1-month visit following initiation of treatment. The study patient underwent standard treatment for neurosyphilis. RESULTS: Ophthalmic examination and imaging studies were consistent with the diagnosis of ASPPC. The patient age was 33 year-old and the baseline visual acuity was 20/400 and 20/80 in the right and left eyes, respectively. At presentation, SD-OCT scans showed disruption and loss of the ellipsoid zone (EZ), small nodular elevations on retinal pigment epithelium (RPE) and punctate hyperreflectivity in the choroid. Enface OCT at the level of RPE and EZ demonstrated multiple hyperreflective dot-like lesions simmetrically distributed within the macular area. These dot-like lesions corresponded to the small nodular elevations on RPE and to disruption/loss of EZ observed with SD-OCT. One month after neurosyphilis therapy, the visual acuity improved and the outer retinal changes partially reversed in both eyes. CONCLUSIONS: We report the outer retinal findings and its correlation using both en-face and SD-OCT in a patient with ASPPC. En-face OCT imaging provides a more precise outer retinal layers analyses allowing a better understanding of the ASPPC pathophysiology.

CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

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.

Fusion proteins for treatment of retinal diseases: aflibercept, ziv-aflibercept, and conbercept.

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.

New associations of classic acute macular neuroretinopathy.

PURPOSE: To describe novel underlying associations of classic acute macular neuroretinopathy (AMN). METHODS: Multimodal imaging case series evaluating patients with classic AMN lesions and previously unreported underlying aetiologies. RESULTS: Six patients were included (five women, one man, mean age 30±7 years). Mean distance best corrected visual acuity at initial presentation was 0.21±0.3 logMAR (mean Snellen acuity: 20/30, range 20/15-20/100) and at last follow-up visit 0.09±0.17 logMAR (Snellen acuity: 20/20, range 20/15-20/60). All cases but one had bilateral lesions and showed typical parafoveal hyporeflective lesions on infrared imaging, which corresponded to the hyper-reflectivity in the Henle's layer with attenuation of the external limiting membrane, the ellipsoid zone and interdigitation zone. Underlying diseases included thrombocytopenia and anaemia associated with dengue fever, acute lymphoblastic leukaemia, chronic kidney disease and ulcerative colitis, while Valsalva-like manoeuvre was found to be a potential trigger. Other novel associations included the use of lisdexamphetamine. CONCLUSIONS: Classic AMN may be associated with leukaemia, dengue fever, ulcerative colitis and chronic kidney disease, probably as a result of chorioretinal hypoxia in the setting of thrombocytopenia and anaemia. Adrenergic agonists such as lisdexamphetamine may also contribute to the manifestation of AMN.