Predictors of disease course and long-term outcomes of idiopathic intracranial hypertension in children and adolescents.

This study aimed to identify predictors for unfavorable disease course and clinical and visual outcomes in pediatric patients with idiopathic intracranial hypertension (IIH). Employing a multi-tiered approach, we retrospectively analyzed clinical, ophthalmic, and neuroimaging data from patients diagnosed with IIH between 2003 and 2021. Of the 97 patients included, 56 (58%) were females. The median age was 12 years [Interquartile range (IQR) 9, 14], and the median follow-up time was 39.0 months (IQR 14.8, 90.9). Forty-two (43%) patients had an unfavorable disease course, 28 (29%) had persistence of headache at last follow-up, and 16 (18%) had a poor visual outcome, most of them with mild visual disturbances. Poor visual outcome was more common in females compared to males [16/47 (34%) vs. 0/39, p < 0.001)]. On multivariate regression analysis, female sex and disease recurrence were significantly associated with poor visual outcomes (OR: 18.5, CI:1.3-270, P = 0.03, and OR: 5.1, CI: 1.2-22.5, P = 0.03, respectively). Patients with persistent headaches exhibited lower incidence of papilledema, lower opening pressure, and fewer neuroimaging markers indicating elevated intracranial pressure. CONCLUSIONS: This study provides insights into predictive factors for an unfavorable disease course, persistent headaches, and poor visual outcomes in patients with childhood IIH. Patients with persistent headaches may have a variant of a chronic pain syndrome warranting a different therapeutic approach. WHAT IS KNOWN: • Childhood-onset Idiopathic Intracranial hypertension (IIH) is a heterogenous disease. The knowledge on disease trajectory and long-term outcomes and its predictors is limited. WHAT IS NEW: • A higher opening pressure and factors suggestive of the metabolic syndrome predict an unfavorable disease course whereas female sex and disease recurrence are significantly associated with poor visual outcomes • A third of the patients diagnosed with IIH experience ongoing headaches despite achieving favorable visual outcomes. This subset, characterized by lower disease-severity indicators at onset may represent a distinct subgroup warranting a different therapeutic approach.

Sleep Disturbances in Adolescents With Idiopathic Intracranial Hypertension.

BACKGROUND: We aimed to assess the presence of sleep disturbances in adolescents with idiopathic intracranial hypertension (IIH) and to determine whether demographic, anthropometric, and clinical factors are associated with disrupted sleep. METHODS: Sleep disturbances and patterns were evaluated in a cohort of adolescents (aged 12 to 18 years) with ongoing IIH and compared with a healthy age- and sex-matched control group. All participants responded to three self-rating questionnaires: the School Sleep Habits Survey (SSHS), the Pediatric Sleep Questionnaire (PSQ), and the Depression, Anxiety, and Stress Scale. The study group's demographic, clinical, laboratory, and radiological data were documented, and their association with sleep patterns was examined. RESULTS: Thirty-three adolescents with ongoing IIH and 71 healthy controls were included. There was a significantly higher prevalence of sleep disturbances in the IIH group compared with the controls (SSHS, P < 0.001 and PSQ, P < 0.001), as well as of their independent subscales: sleep-related breathing disorders (P = 0.006), daytime sleepiness (P = 0.04), sleep/wake disruptions (P < 0.001), and sleep-related depressive tendencies (P < 0.001). According to subgroup analyses, these differences were also present between the normal-weight adolescents but not between the overweight IIH and control adolescents. No differences were found in the demographic, anthropometric, and IIH disease-related clinical measures between individuals with IIH with disrupted and normal sleep patterns. CONCLUSIONS: Sleep disturbances are common among adolescents with ongoing IIH, irrespective of their weight and disease-related characteristics. Screening adolescents with IIH for sleep disturbances is recommended as part of their multidisciplinary management.

Regenerative Effect of Adipose Derived Mesenchymal Stem Cells on Ganglion Cells in the Hypoxic Organotypic Retina Culture.

Background and Objectives: To examine whether ischemic retinal ganglion cells (RGCs) will be salvaged from cell death by human adipose-derived mesenchymal stem cells (ADSCs) in an organotypic retina model. Methods and Results: Deprived of arterial oxygen supply, whole mice retinas were cultured as an ex vivo organotypic cultures on an insert membrane in a 24-well plate. The therapeutic potential of ADSCs was examined by co-culture with organotypic retinas. ADSCs were seeded on top of the RGCs allowing direct contact, or at the bottom of the well, sharing the same culture media and allowing a paracrine activity. The number of surviving RGCs was assessed using Brn3a staining and confocal microscopy. Cytokine secretion of ADSCs to medium was analyzed by cytokine array. When co-cultured with ADSCs, the number of surviving RGCs was similarly significantly higher in both treatment groups compared to controls. Analysis of ADSCs cytokines secretion profile, showed secretion of anti-apoptotic and pro-proliferative cytokines (threshold＞1.4). Transplantation of ADSCs in a co-culture system with organotypic ischemic retinas resulted in RGCs recovery. Since there was no advantage to direct contact of ADSCs with RGCs, the beneficial effect seen may be related to paracrine activity of ADSCs. Conclusions: These data correlated with secretion profile of ADSCs' anti-apoptotic and pro-proliferative cytokines.

Short-Term Vision-Related Ocular Side Effects of Treatment with Dexmethylphenidate for Attention-Deficit/Hyperactivity Disorder.

Objective: To evaluate the short-term effect of dexmethylphenidate (D-MPH) on visual acuity (VA), pupil size, anterior chamber depth, and accommodation-convergence reflex in children treated with D-MPH for attention-deficit/hyperactivity disorder (ADHD). Method: Prospective cohort study including 15 patients aged 8-16 (11.58 ± 2.39) treated with D-MPH for ADHD. Patients were questioned for subjective complaints such as blurred vision and photosensitivity. An ophthalmic evaluation was performed twice; before and 1.5 hours after D-MPH administration. The examination included evaluation of best corrected visual acuity at distance and near, accommodation range, convergence range, 3D vision test (stereopsis), and anterior segment optical coherence tomography. Results: A significant association between change in pupil diameter and D-MPH treatment dose was demonstrated (p = 0.01). In addition, a positive correlation between complaints about blurred vision and pupil's size change was found (p < 0.05). There were no significant changes in VA, convergence range, stereopsis, accommodation range, or anterior chamber measures. Conclusions: Our findings provide support for the effect of stimulants on pupil diameter in a dose-dependent manner. No clinically significant differences in visual functions were found 1.5 hours after consumption of D-MPH. Institutional review board clinical trial refference no. 0122-17-TLV.

Elevated lumbar puncture opening pressure in aseptic meningitis.

OBJECTIVES: Elevated lumbar puncture opening pressure (ELPOP) is a reported but understudied phenomenon in aseptic meningitis. This study aimed to characterize the features of ELPOP in aseptic meningitis patients. METHODS: An observational, retrospective, single-center study was conducted. We included all adult patients diagnosed with aseptic meningitis or meningoencephalitis from October 2015 to May 2017, for whom lumbar puncture opening pressure (LP OP) was measured. OP > 25 cm H2O was documented as ELPOP. Patients' demographic characteristics, clinical data, laboratory and cerebrospinal fluid (CSF) results, as well as optic disc appearance were analyzed. RESULTS: Among 116 patients (61 males) included, 16 patients (14 %) had ELPOP (11 males). The average age of those patients was 32.4 years (SD = 9.8), and the mean OP was 31.7 cm H2O (SD = 6.02) as opposed to the mean normal LPOP (NLPOP) of16.13 cm H2O (SD = 4.15). Body mass index (BMI) was significantly higher in the ELPOP group (p = 0.0081). Funduscopic examination was documented in 15/16 patients in the ELPOP group and revealed swollen optic discs in 6 (40 %) patients. Fundus examination was performed in 62 patients in the NLPOP group, of whom 2 (3.2 %) had a swollen disc. There was no difference in CSF content between groups. CONCLUSIONS: This study fills the void of information lacking on the frequency of ELPOP in aseptic meningitis. Its association with increased BMI may be related to the pathogenesis. LP OP should be measured in all patients with aseptic meningitis. Additional research is needed to determine the threshold of tolerated intracranial pressure (ICP).

A Consensus Statement on the Terminology for Automated Visual Field Abnormalities.

BACKGROUND: A multitude of terms have been used to describe automated visual field abnormalities. To date, there is no universally accepted system of definitions or guidelines. Variability among clinicians creates the risk of miscommunication and the compromise of patient care. The purposes of this study were to 1) assess the degree of consistency among a group of neuro-ophthalmologists in the description of visual field abnormalities and 2) to create a consensus statement with standardized terminology and definitions. METHODS: In phase one of the study, all neuro-ophthalmologists in Israel were asked to complete a survey in which they described the abnormalities in 10 selected automated visual field tests. In phase 2 of the study, the authors created a national consensus statement on the terminology and definitions for visual field abnormalities using a modified Delphi method. In phase 3, the neuro-ophthalmologists were asked to repeat the initial survey of the 10 visual fields using the consensus statement to formulate their answers. RESULTS: Twenty-six neuro-ophthalmologists participated in the initial survey. On average, there were 7.5 unique descriptions for each of the visual fields (SD 3.17), a description of only the location in 24.6% (SD 0.19), and an undecided response in 6.15% (SD 4.13). Twenty-two neuro-ophthalmologists participated in the creation of a consensus statement which included 24 types of abnormalities with specific definitions. Twenty-three neuro-ophthalmologists repeated the survey using the consensus statement. On average, in the repeated survey, there were 5.9 unique descriptions for each of the visual fields (SD 1.79), a description of only the location in 0.004% (SD 0.01), and an undecided response in 3.07% (SD 2.11%). Relative to the first survey, there was a significant improvement in the use of specific and decisive terminology. CONCLUSIONS: The study confirmed a great degree of variability in the use of terminology to describe automated visual field abnormalities. The creation of a consensus statement was associated with improved use of specific terminology. Future efforts may be warranted to further standardize terminology and definitions.

Radiologically isolated aquaporin-4 antibody neuromyelitis optica spectrum disorder.

Aquaporin-4 antibody (AQP4-Ab) Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare neuroinflammatory syndrome presenting predominantly with optic neuritis and transverse myelitis. We report a case of radiologically isolated longitudinally extensive optic neuritis in an asymptomatic 12-year-old female with positive serum AQP4-Ab, with resolution of imaging changes after immune therapy. By contrast to patients with radiologically isolated syndrome, of which some will never convert to multiple sclerosis, the pathogenicity of AQP4-Ab in the context of sub-clinical disease, supported treatment in our patient. Given the severe morbidity in AQP4-Ab NMOSD, prognostic biomarkers for disease severity are required to guide optimal therapy for patients.

Acinar Atrophy, Fibrosis and Fatty Changes Are Significantly More Common than Sjogren's Syndrome in Minor Salivary Gland Biopsies.

Background and Objective: Hyposalivation and xerostomia can result from a variety of conditions. Diagnosis is based on a combination of medical history, clinical and serological parameters, imaging, and minor salivary gland biopsy when indicated. The Objective was to characterize microscopic changes in minor salivary gland biopsies taken in patients with xerostomia. Materials and Methods: 10-year retrospective analysis of minor salivary gland biopsies, 2007-2017. Histomorphometric analysis included gland architecture, fibrosis, fat replacement, inflammation and stains for IgG/IgG4, when relevant. Results: 64 consecutive biopsies, of which 54 had sufficient tissue for diagnosis of Sjogren's Syndrome (SS) were included (18 males, 46 females, average age 56 (±12.5) years). Only 12 (22.2%) were microscopically consistent with SS, none stained for IgG4. Medical conditions were recorded in 40 (63%), most frequently hypertension and hyperlipidemia (28% each). Medications were used by 45 (70%), of which in 50% more than one. Xerostomia in non-SS cases was supported by abnormal gland morphology, including acinar atrophy, fibrosis and fatty replacement. All morphological abnormalities are correlated with age, while fatty replacement correlated with abnormal lipid metabolism. Multiple medications correlated with microscopic features which did not correspond with SS. Conclusions: SS was confirmed in a minority of cases, while in the majority fatty replacement, fibrosis and multiple medications can explain xerostomia, and are related to aging and medical conditions. Medical history and auxiliary tests could lead to correct diagnosis in non-SS patients, avoiding biopsy. The necessity of a diagnostic biopsy should be given serious consideration only after all other diagnostic modalities have been employed.

Peripapillary hyperreflective ovoid mass-like structures-a novel entity as frequent cause of pseudopapilloedema in children.

BACKGROUND: Optic nerve head drusen (ONHD) are considered the most common cause for pseudopapilloedema in children. We aimed to investigate and further characterize a new type of optic nerve head lesion on enhanced depth imaging optical coherence tomography (EDI-OCT) named peripapillary hyperreflective ovoid mass-like structures (PHOMS), and ONHD in asymptomatic children with pseudopapilloedema. METHODS: Retrospective cohort study including 64 eyes from 32 patients with pseudopapilloedema due to PHOMS and/or ONHD. Mean age was 9.0 ± 3.1 years. PHOMS and ONHD were identified and classified on EDI-OCT and infrared images. Ultrasound images were classified for the presence of hyperechogenic structures of the optic nerve head. RESULTS: On EDI-OCT, PHOMS were detected in 63 out of 64 eyes (98.4%). In 60 eyes (93.8%), small hyperreflective foci inside the PHOMS were present. In all cases, we identified a new ring sign visible on infrared images, corresponding clearly to the edge of the PHOMS as seen on EDI-OCT. On ultrasound, we describe a new feature of PHOMS appearing as small hyperechogenic structures without posterior shadowing. In 13 eyes (20.3%), ONHD were present on EDI-OCT and ultrasound. CONCLUSION: This is the first study showing that PHOMS are the most common cause for pseudopapilloedema in children. PHOMS is a new entity of optic nerve head lesions. It might be a precursor of buried optic nerve head drusen, which can lead to visual field defects, haemorrhages and CNV. This study offers new tools to identify and follow-up these lesions early in childhood using EDI-OCT.

Visual function tests including the role of optical coherence tomography in neurofibromatosis 1.

Optic pathway glioma (OPG) is a common and significant complication of neurofibromatosis 1 (NF-1) that might lead to vision loss. The main reason to treat OPG is to preserve vision. Tumor location along the visual pathway largely dictates the presenting signs and symptoms. Clinical ophthalmic evaluation is focused on optic nerve functions including evaluation of pupils' reaction to light, visual acuity, color vision, and visual field, as well as optic nerve appearance. An important relatively new ancillary test is optic coherence tomography (OCT) that measures the volume of retinal nerve fiber layer around the optic nerve and the ganglion cell layer-inner plexiform layer (GCL-IPL) of the macula, both proved to be strongly associated with losing vision in OPG. Accurate evaluation of vision functions plays a critical role in the decision of treatment. In this review, we describe the ophthalmological assessment including new biomarkers in clinical use. We also outline prognostic factors and current recommendations for surveillance and indications for treatment.

The great imitator on the rise: ocular and optic nerve manifestations in patients with newly diagnosed syphilis.

PURPOSE: Ocular manifestations of syphilis have been reported in 2-10% of systemic infection. The purpose of this study was to report the incidence of ocular syphilis and various ocular manifestations, particularly optic nerve involvement, in newly diagnosed cases. METHODS: This was a retrospective study. Medical records of newly diagnosed syphilis patients between January 2009 and January 2017 in a tertiary medical centre were reviewed. RESULTS: There were 123 new systemic syphilis cases out of 569,222 (0.02%) admissions to the Tel Aviv Medical Center during the study period. Ninety-three of the 123 patients (76%) underwent ophthalmological examination. Twenty-three of the 93 patients (25%, mean age 48.6 ± 12.9 years, 20 males) had ocular syphilis, and in 12/23 (52%) patients, the ocular symptoms and findings prompted syphilis investigation. Eighteen of the 23 (78%) had optic nerve involvement, and the most common was inflammatory disc oedema. Older age (p = 0.0005) and tertiary stage disease (p = 0.0441) were associated with ocular manifestations and the presence of optic nerve findings. Human immunodeficiency virus (HIV) was associated with ocular but not optic nerve findings. Treatment included intravenous penicillin G, and four patients with severe optic neuropathy were also treated with systemic corticosteroids. Visual acuity significantly improved in most patients (p < 0.05). CONCLUSION: Ocular syphilis was found in one-quarter of the patients diagnosed with systemic syphilis and preceded the diagnosis of systemic disease in one-half of them. Optic nerve involvement was a common manifestation. A high index of suspicion for Treponema infection is required in patients presenting with optic nerve involvement to facilitate prompt diagnosis and treatment. Post-treatment visual outcome was good.

Familial Occurrence of Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology. Its occurrence in the general population is 1/100,000, and 20/100,000 among overweight women of childbearing age. Familial occurrence is reportedly uncommon and not well-characterized. OBJECTIVES: To describe a familial association with IIH. METHODS: We conducted a retrospective chart review of all familial cases of IIH examined in the neuro-ophthalmology clinic of our medical center between January 2006 and June 2013. RESULTS: Of a total of 520 patients with IIH, 15 had other family members with IIH (from seven different families). The family relation was a mother and daughter in two families, a brother and sister in four families, and an aunt and two first-degree cousins in the seventh family. Symptoms, course of disease, and risk factors were similar among the relatives of all seven families, except for the age at diagnosis, which was different in one family. All of the adult patients of six families were obese (body mass index 25-35 kg/m2), and all of the members of the other family were morbidly obese. There was no association between other systemic risk factors and IIH. CONCLUSIONS: IIH occurrence within a family is more common than previously believed, and its incidence in families is more common than in the general population. The clinical course appears to be similar in family members. Our findings suggest a genetic predisposition. Further investigation of familial cases may yield useful information on the pathogenesis and genetic nature of this condition.

Reduced Suprathreshold Odor Identification in Patients with Pseudotumor Cerebri: A Non-Randomized Prospective Study.

BACKGROUND: Recent evidence suggests that olfaction is impaired in patients with pseudotumor cerebri (PTC). OBJECTIVES: To measure suprathreshold olfactory function by using the University of Pennsylvania Smell Identification Test (UPSIT), assessing its usefulness for routine clinical use. METHODS: Forty PTC patients underwent USPIT olfactory testing. RESULTS: Twenty-nine out of 40 (73%) PTC patients (36 women, 4 men; mean age 34 years) had reduced suprathreshold smell sensation according to UPSIT scores: 19 (47%) had mild microsmia, 9 (23%) had moderate microsmia, and one (3%) was classified as having severe microsmia. The mean UPSIT score of all patients was 32.4 (95% confidence interval 31.4-33.4). Multivariate regression analysis found that UPSIT scores were not related to disease activity, disease duration, initial intracranial pressure (ICP), or visual function. CONCLUSIONS: Many PTC patients have reduced suprathreshold olfactory dysfunction that can be discovered by UPSIT, a rapidly administered smell test, which is suitable for clinical office use.

The Efficacy of Bilateral Lateral Rectus Recession According to Secondary Deviation Measurements in Unilateral Exotropic Duane Retraction Syndrome.

PURPOSE: To evaluate the surgical results of asymmetric bilateral lateral rectus recession in exotropic Duane retraction syndrome with abnormal face turn toward the opposite side according to secondary deviation measurements. METHODS: Retrospective chart review. RESULTS: Seven cases of unilateral exotropic Duane retraction syndrome were reviewed. All cases had globe retraction on adduction and exotropia with limited adduction, five of which also had mild limitation of abduction. Four cases had upshoot/downshoot on adduction and all patients had face turn. Exotropia was measured in forced primary position. The average lateral rectus recession was 6.36 mm (range: 5.5 to 7.5 mm) in the affected eye and 7.36 mm (range: 6.5 to 8.5 mm) in the healthy eye. The mean follow-up period was 282 days. Mean exotropia in the forced primary position improved from 27.9 ± 5.7 prism diopters (PD) preoperatively to 7.9 ± 16.8 PD postoperatively (P = .025). Head position resolved completely in all but one case (P =.031). There were no significant changes in ductions. CONCLUSIONS: The results suggest that asymmetric bilateral lateral rectus recession in exotropic Duane retraction syndrome with abnormal head turn posture successfully eliminates abnormal head turn posture and exotropia in most cases. [J Pediatr Ophthalmol Strabismus. 2018;55(1):47-52.].

Visual outcomes of laser vision correction in eyes with preoperative amblyopia.

PURPOSE: To evaluate the visual outcomes of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in amblyopic eyes. SETTING: Care Vision Refractive Clinic, Tel Aviv, Israel. DESIGN: Retrospective case series. METHODS: Amblyopic eyes of patients with a preoperative corrected distance visual acuity (CDVA) of 20/33 or worse had PRK or LASIK. Postoperative visual outcomes (uncorrected distance visual acuity, CDVA) and correlations with age, preoperative CDVA, refractive error type, astigmatism grade, procedure type, laser suite model, amblyopia grade, and amblyopia type were analyzed. RESULTS: This study evaluated 327 eyes (327 patients). The CDVA improved more than 1, 2, and 3 Snellen lines in 147 eyes (45.0%), 75 eyes (22.9%), and 32 eyes (9.8%), respectively. Age (P = .007, B = 0.002), and preoperative CDVA (P < .001, B = -0.405) were significantly associated with CDVA improvement. The outcome in eyes with lower myopia was significantly better than in eyes with hyperopia (0.054 logMAR difference; P = .016) or high myopia (0.036 logMAR difference; P = .002). Moderately amblyopic eyes had significantly better visual outcomes than mildly amblyopic eyes (0.038 logMAR difference; P = .001). No significant difference was found between PRK and LASIK (P = .262). CONCLUSIONS: Laser vision correction, regardless of the type of procedure (LASIK or PRK) might improve CDVA in a large portion of amblyopic patients. Improvement was greater in younger patients, eyes with lower initial CDVA, and eyes with lower myopia.

A case report of ophthalmic artery emboli secondary to Calcium Hydroxylapatite filler injection for nose augmentation- long-term outcome.

BACKGROUND: Filler injection for face augmentation is a common cosmetic procedure in the last decades, in our case report we describe long-term outcomes of a devastating complication of ophthalmic artery emboli following Calcium Hydroxylapatite filler injection to the nose bridge. CASE PRESENTATION: A healthy 24-year-old women received a Calcium Hydroxylapatite filler injection to her nose bridge for the correction of nose asymmetry 8 years post rhinoplasty. She developed sudden right eye ocular pain and visual disturbances. Visual acuity was 20/20 in both eyes and visual field in the right eye showed inferior arch with fixation sparing and supero-temporal central scotoma. Examination revealed marked periorbital edema and hematoma, ptosis, ocular movements limitation, an infero-temporal branch retinal artery occlusion and multiple choroidal emboli. Eighteen months post initial presentation ptosis and eye movements returned normal and choroidal emboli absorbed almost completely. However, visual acuity declined to 20/60, visual field showed severe progressive deterioration with a central and supero-nasal field remnant and the optic disc became pallor. CONCLUSION: Cosmetic injection of calcium hydroxylapatite to the nose bridge can result in arterial emboli to the ophthalmic system with optic nerve, retinal and choroidal involvement causing long term severe visual acuity and visual field impairment.

Idiopathic Intracranial Hypertension-A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a well-characterized syndrome, most commonly affecting obese women of childbearing age. Differences in its prevalence have been reported in various populations. The aim of this article was to determine whether differences in clinical presentation and management exist for patients with IIH between different regions the world. METHODS: Retrospective database analysis of adult patients with IIH from 4 different neuro-ophthalmology clinics. The data collected included gender, age of onset, body mass index (BMI), lumbar puncture opening pressure, initial visual acuity (VA), initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, final VA, and final VF MD. RESULTS: The study population consisted of 244 patients, with significant regional variations of female to male ratio. Overall, there was no significant difference regarding the age of diagnosis or the BMI. Acetazolamide was the first line of treatment in all groups but there was a difference between countries regarding second-line treatment, including the use of surgical interventions. Mean initial VA differed between groups but the final change in VA was the same among all the study groups. CONCLUSIONS: There are differences in IIH presentation, treatment, and response to therapy among different countries. International prospective studies involving multiple centers are needed to determine the potential influence of environmental and genetic factors on the development of IIH and to improve the management of this potentially blinding disorder.

Therapeutic Monoclonal Antibodies and Fragments: Bevacizumab.

Bevacizumab (Avastin) is a recombinant humanized monoclonal immunoglobulin antibody that has two antigen-binding domains and blocks all active forms of vascular endothelial growth factor-A. It was originally designed and is still in use as antitumor agent (for colorectal and non-small cell lung cancers). Besides inhibiting vessel growth and neovascularization, the drug promotes the regression of existing microvessels and induces 'normalization' of surviving mature vasculature, stabilizes vessels and prevents leakage. Its molecular weight is 149 kDa and its estimated terminal half-life is approximately 20 days for both men and women. The effectiveness and safety of bevacizumab was proven in retrospective and prospective controlled clinical trials for the treatment of neovascular age-related macular degeneration, neovascularization in proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusion and retinopathy of prematurity, especially for zone I. Uncontrolled trials have shown its effectiveness in various other conditions as myopic and uveitic choroidal neovascularization and neovascular glaucoma. There are no absolute contraindications to intravitreal injection though it is recommended to withhold treatment in patients who have recently suffered from a cardiovascular or cerebrovascular event and during pregnancy. Ocular complications from intravitreal use are usually mild and transient (corneal abrasion, chemosis, subconjunctival hemorrhage and vitreous hemorrhage). Bacterial endophthalmitis is rare (about 0.1%). New or progressive subretinal hemorrhages, tears of the retinal pigment epithelium and an increased incidence of geographic atrophy have also been reported.