This document provides information about the intraocular safety of anti-VEGF agents:
- Aflibercept has a well-established safety profile across clinical trials and real-world use, with rare rates of intraocular inflammation (IOI), endophthalmitis, and retinal vasculitis reported.
- Recent communications from the American Society of Retina Specialists (ASRS) have reported cases of IOI and occlusive retinal vasculitis following administration of brolucizumab.
- A review of safety data from trials of brolucizumab found higher rates of serious ocular adverse events like IOI compared to aflibercept, raising concerns about its intraocular safety profile
Retinal vein occlusions are the second most common retinal vascular disease after diabetic retinopathy. Several studies have evaluated treatments for macular edema secondary to retinal vein occlusions. Anti-VEGF drugs like ranibizumab, aflibercept, and bevacizumab have been shown to significantly improve visual acuity and reduce macular thickness compared to observation or laser, with benefits maintained over 1-2 years. Dexamethasone intravitreal implants also provide initial benefits but effects are not sustained long-term and are associated with increased risks of cataract and elevated intraocular pressure.
Boris Malyugin, M.D., PhD.'s presentation about Malyugin Ring® pearls. The key learning points of the presentation include the step-wise approach in managing small pupils, the main drivers for the decision to use pupil expander device, and the Malyugin Ring® implantation and removal pearls.
The document discusses the Hess chart, which is used to map eye movements and diagnose extraocular muscle palsies. It describes how Hess developed the chart in 1908 and won a Nobel Prize for his work mapping the brain's control of internal organs. The document outlines how the Hess chart is performed and interpreted, including identifying underacting and overacting muscles, differentiating comitant from incomitant strabismus, and aiding in surgical planning. Several examples of Hess chart interpretations are provided to demonstrate identifying affected muscles and diagnosing conditions like third nerve palsy and Brown's syndrome.
This document provides information on:
1. The anatomy and actions of the extraocular muscles, including their blood supply and concept of arc of contact.
2. The general goals and pre-operative assessment of strabismus surgery.
3. Anatomical considerations and different types of strabismus surgeries including muscle weakening and strengthening procedures. Detailed descriptions of recession, resection, transpositions and other techniques are provided.
This document presents a case study of intermittent exotropia in a 3-year-old female patient. On examination, the patient was found to have an alternating exotropia when measuring the angle of deviation at distance and near. She was diagnosed with intermittent exotropia. For treatment, the patient underwent 6 weeks of patching therapy and showed orthotropia on follow up visits. She later underwent bilateral lateral rectus recession surgery, with good control of exotropia observed at subsequent reviews. The document also provides background information on intermittent exotropia including prevalence, etiology, symptoms, classification, evaluation, treatment options, and surgical outcomes.
This document provides an overview of macular holes, including:
- Classification into primary (idiopathic) and secondary holes. Primary holes are caused by vitreous traction while secondary have other causes like trauma.
- Stages of macular hole formation based on Gass classification from early detachment to full thickness hole.
- Surgical treatment involves vitrectomy to relieve traction along with internal limiting membrane peeling which has good outcomes in improving vision.
- Differential diagnosis includes epiretinal membranes and pseudoholes which have different presentations and prognoses.
Bevacizumab and ranibizumab in ROP-0- AJAY DUDANIAjayDudani1
Bevacizumab and ranibizumab are anti-VEGF drugs used to treat retinopathy of prematurity (ROP). A study compared outcomes of 72 eyes treated with either bevacizumab or ranibizumab and found both drugs were effective in treating ROP. However, bevacizumab has a longer half-life and can suppress VEGF levels systemically, raising concerns about potential pulmonary and other side effects in premature infants. Another study detected bevacizumab in the serum of infants with ROP for up to 60 days post-injection. Ranibizumab has a shorter half-life and studies found it effectively treated ROP with no reported systemic effects. Overall, the document discusses comparative pharmacological
Retinal vein occlusions are the second most common retinal vascular disease after diabetic retinopathy. Several studies have evaluated treatments for macular edema secondary to retinal vein occlusions. Anti-VEGF drugs like ranibizumab, aflibercept, and bevacizumab have been shown to significantly improve visual acuity and reduce macular thickness compared to observation or laser, with benefits maintained over 1-2 years. Dexamethasone intravitreal implants also provide initial benefits but effects are not sustained long-term and are associated with increased risks of cataract and elevated intraocular pressure.
Boris Malyugin, M.D., PhD.'s presentation about Malyugin Ring® pearls. The key learning points of the presentation include the step-wise approach in managing small pupils, the main drivers for the decision to use pupil expander device, and the Malyugin Ring® implantation and removal pearls.
The document discusses the Hess chart, which is used to map eye movements and diagnose extraocular muscle palsies. It describes how Hess developed the chart in 1908 and won a Nobel Prize for his work mapping the brain's control of internal organs. The document outlines how the Hess chart is performed and interpreted, including identifying underacting and overacting muscles, differentiating comitant from incomitant strabismus, and aiding in surgical planning. Several examples of Hess chart interpretations are provided to demonstrate identifying affected muscles and diagnosing conditions like third nerve palsy and Brown's syndrome.
This document provides information on:
1. The anatomy and actions of the extraocular muscles, including their blood supply and concept of arc of contact.
2. The general goals and pre-operative assessment of strabismus surgery.
3. Anatomical considerations and different types of strabismus surgeries including muscle weakening and strengthening procedures. Detailed descriptions of recession, resection, transpositions and other techniques are provided.
This document presents a case study of intermittent exotropia in a 3-year-old female patient. On examination, the patient was found to have an alternating exotropia when measuring the angle of deviation at distance and near. She was diagnosed with intermittent exotropia. For treatment, the patient underwent 6 weeks of patching therapy and showed orthotropia on follow up visits. She later underwent bilateral lateral rectus recession surgery, with good control of exotropia observed at subsequent reviews. The document also provides background information on intermittent exotropia including prevalence, etiology, symptoms, classification, evaluation, treatment options, and surgical outcomes.
This document provides an overview of macular holes, including:
- Classification into primary (idiopathic) and secondary holes. Primary holes are caused by vitreous traction while secondary have other causes like trauma.
- Stages of macular hole formation based on Gass classification from early detachment to full thickness hole.
- Surgical treatment involves vitrectomy to relieve traction along with internal limiting membrane peeling which has good outcomes in improving vision.
- Differential diagnosis includes epiretinal membranes and pseudoholes which have different presentations and prognoses.
Bevacizumab and ranibizumab in ROP-0- AJAY DUDANIAjayDudani1
Bevacizumab and ranibizumab are anti-VEGF drugs used to treat retinopathy of prematurity (ROP). A study compared outcomes of 72 eyes treated with either bevacizumab or ranibizumab and found both drugs were effective in treating ROP. However, bevacizumab has a longer half-life and can suppress VEGF levels systemically, raising concerns about potential pulmonary and other side effects in premature infants. Another study detected bevacizumab in the serum of infants with ROP for up to 60 days post-injection. Ranibizumab has a shorter half-life and studies found it effectively treated ROP with no reported systemic effects. Overall, the document discusses comparative pharmacological
This document summarizes key aspects of sensory evaluation of squint or strabismus. It begins by describing normal binocular development and vision, including the development of binocular fusion and stereopsis in infants. It then discusses abnormal binocular vision including sensory adaptations like suppression, anomalous retinal correspondence, and eccentric fixation. Finally, it outlines several tests used to evaluate the sensory system in strabismus, including visual acuity tests, Worth four-dot test, Bagolini striated glasses, 4 prism base out test, synaptophore, and after-image tests.
Macular Degeneration - Update on clinical trial results and new treatmentspresmedaustralia
The CATT study found that ranibizumab (Lucentis) and bevacizumab (Avastin) produced similar visual acuity outcomes for wet AMD over 2 years. However, bevacizumab was less effective in reducing retinal swelling. There were also more serious systemic side effects with bevacizumab. While deaths, heart attacks and strokes were low with both drugs, CATT was not large enough to determine if there were meaningful differences in these rare but serious side effects. More research is still needed to determine longer term safety and efficacy.
This document discusses retinal breaks and retinal detachment. Some key points:
- Retinal breaks can cause retinal detachment and occur in about 6% of the population, with retinal detachment occurring in around 0.07% of people in their lifetime.
- Common causes of retinal breaks include trauma, vitreous traction, and increasing age. Symptoms may include floaters, photopsias, and vitreous hemorrhage.
- Examination involves slit lamp biomicroscopy and sometimes B-scan ultrasound or vitrectomy. Certain lesions like retinal dialysis, horseshoe tears, and operculated tears often warrant treatment to prevent retinal detachment, while smaller lesions may not require intervention
The document discusses various causes and clinical approaches to evaluating proptosis in adults. Common causes in adults include thyroid eye disease, pseudotumor, orbital cellulitis, trauma, meningioma, lymphoma, and cavernous hemangioma. A thorough history, examination, and imaging studies are needed to differentiate between causes and guide treatment.
ULTRASONOGRAPHY (USG) AND ULTRASOUND BIOMICROSCOPY(UBM)Dr. Gaurav Shukla
Ultrasonography and ultrasound biomicroscopy are important tools for diagnosing ocular and orbital abnormalities. Ultrasonography uses high frequency sound waves transmitted into the eye via a probe to image intraocular structures. A-scans display returning echoes in one dimension while B-scans create a two-dimensional image by accumulating A-scan echoes. B-scans are useful for evaluating lesions' topography, reflectivity, internal structure, and mobility. Common applications include detecting retinal detachments, vitreous opacities, intraocular tumors, and foreign bodies. Ultrasonography is valuable for screening and characterizing many ocular pathologies.
This document discusses intravitreal injections for drug delivery to the posterior segment of the eye. It begins by explaining the challenges of drug delivery due to the blood-ocular barrier and how sustained release systems and nano-particles were developed. It then provides details on the procedure of intravitreal injection, including indications, agents used, aseptic technique, complications, and anti-VEGF agents like bevacizumab, ranibizumab, pegaptanib, and aflibercept.
This document provides an outline and overview of lamellar keratoplasty techniques. It discusses the anatomy of the cornea and indications for lamellar keratoplasty such as keratoconus. Anterior lamellar keratoplasty techniques include deep anterior lamellar keratoplasty (DALK) using the big bubble technique or Melle's technique to remove the corneal stroma down to Descemet's membrane. Posterior lamellar keratoplasty techniques like Descemet's stripping endothelial keratoplasty (DSEK) are also summarized. Complications of lamellar keratoplasty procedures and advantages over penetrating keratoplasty are highlighted.
This document discusses techniques for managing a small pupil during cataract surgery. Small pupils are defined as less than 4mm in diameter and can increase risks of complications during surgery. Medications like Flomax and glaucoma medications can cause miosis preoperatively. Intracameral lidocaine and epinephrine or Omidria can help maintain pupil size during surgery. For small, floppy pupils, iris hooks, retractors, or expansion rings can be used. For small, stiff pupils, mechanical stretching techniques may work better. Proper pupil management techniques can help reduce surgical risks in patients with small pupils.
The document discusses the evaluation of strabismus. It defines strabismus and the different types such as phoria, tropia, comitant, and incomitant. It describes the history to obtain and various tests used in the examination including motor function tests like cover test, versions, and ductions, and sensory tests like Worth 4-dot and Bagolini lenses. The document provides details on the order and components of a complete ocular examination for strabismus.
The document discusses recent advances in the management of obstruction of the lacrimal drainage system. It describes the history and evolution of various surgical techniques for treating this obstruction, including external dacryocystorhinostomy (DCR), endoscopic endonasal DCR, ultrasonic endoscopic DCR, non-laser endonasal DCR, endocanalicular laser DCR, and balloon-assisted DCR. It then provides details on the surgical procedure for external DCR, including patient preparation, instrumentation, osteotomy creation, flap formation, flap anastomosis, wound closure, and post-operative management. Potential complications are also briefly mentioned.
This document discusses the diagnosis and management of superior oblique palsy. It begins by describing the anatomy and function of the superior oblique muscle. Superior oblique palsy can result in hypertropia, excyclotorsion, and esotropia that are greater in certain gazes. Causes may be congenital or acquired from trauma or vascular issues. Diagnosis involves evaluating eye movements, diplopia, and head tilt. Non-surgical treatment includes patching or prisms while surgery involves weakening the antagonist inferior oblique muscle or tucking the superior oblique tendon. The goal of treatment is to expand the field of single vision while minimizing complications.
This case study describes a child with congenital cataracts who underwent multiple surgeries and treatments over several years. By age 11, the child had developed severe vision loss with only light perception vision in the right eye and 20/200 vision in the left eye. Visual field loss progressed significantly over time. Low vision recommendations evolved from stand magnifiers and telescopes to focus on braille, audiobooks, screen reading software, and closed circuit television to help the child continue their education despite declining vision.
This document discusses fundus examination and its importance in ophthalmology. Fundus examination can detect signs of circulatory, metabolic, and neurological disorders. It is used to identify and locate retinal and optic nerve defects caused by eye disease or trauma, examine the extent of abnormalities to plan treatment, and evaluate treatment success. The document describes different methods of performing fundus examination including direct ophthalmoscopy, indirect ophthalmoscopy, and indirect slit lamp biomicroscopy. It provides examples of common fundus findings and conditions that can be assessed via this examination.
This document provides an overview of branched retinal vein occlusion (BRVO). It discusses the classification, epidemiology, risk factors, pathogenesis, signs and symptoms, diagnostic evaluation, and management of BRVO. Key points include that BRVO is the most common type of retinal vein occlusion and risk factors include hypertension, glaucoma, hyperlipidemia, and advancing age. Diagnostic testing includes fluorescein angiography and OCT to evaluate for macular edema, capillary nonperfusion, and neovascularization. Laser photocoagulation and anti-VEGF injections are common treatment approaches for complications such as macular edema.
Branched Retinal Vein Occlusion (BRVO) for undergraduate MBBS Students.
Covers the basics of Aetiology, pathophysiology, clinical features, types, associated conditions and management of BRVO.
Also encompasses salient points for PGMEE
This document discusses rhegmatogenous retinal detachment (RRD), which occurs when there is a full-thickness defect in the retina allowing fluid from the vitreous to enter the subretinal space. RRD is usually preceded by posterior vitreous detachment. The pathogenesis involves dynamic vitreoretinal traction and predisposing peripheral retinal degeneration. Common predisposing factors are lattice degeneration and retinal tears caused by vitreous traction. Management options include scleral buckling surgery, pneumatic retinopexy, and pars plana vitrectomy, with the goal of identifying and closing all retinal breaks.
This document discusses perimetry and visual field testing. It defines visual field as the area that can be seen at a given moment. There are various methods of visual field testing including kinetic and static perimetry. Automated static perimetry tests like Humphrey and Octopus are now commonly used and test the threshold light intensity that can be detected at different points in the visual field. The results are analyzed based on total deviation plots, pattern deviation plots and global indices to detect and monitor glaucomatous visual field defects. Common patterns of visual field defects seen in different conditions are also described.
A case of dense nuclear cataract has undergone phacoemulsificaton by horizontal chop technique. the pupil was small so Iris retractor was utilized. Intraocular lens was implanted.
The document discusses implantable contact lenses (ICL) for correcting high refractive errors. Key points include:
- ICL is preferred over LASIK for high myopia or thin corneas, as it has fewer risks of complications.
- ICL is made of a biocompatible collamer material and is implanted in the posterior chamber behind the iris.
- A clinical trial found nearly 60% of eyes achieved 20/20 vision and 95% achieved 20/40 vision or better after 3 years with ICL implantation.
- Complications are generally low but can include cataracts, increased eye pressure, damage to the natural lens, and other rare issues like infections. Most risks are
This document discusses idiopathic juxtafoveolar telangiectasia (IJFT), including its classification and stages. It describes IJFT types 1 and 2, with type 1 being congenital and aneurysmal and type 2 being acquired and perifoveal. Type 2 is further classified into 5 stages based on angiographic and imaging findings. The document also presents three case studies where anti-VEGF therapy with ranibizumab was used to treat neovascularization associated with types 1 and 2 IJFT, showing improvements in leakage and vision. While anti-VEGF therapy may help reduce leakage, preexisting photoreceptor damage from IJFT may limit improvements in visual acuity.
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANIAjayDudani1
1) Ranibizumab is the preferred molecule for treating neovascular AMD due to the extensive evidence from numerous clinical trials proving its long-term safety and efficacy compared to alternatives like biosimilars which have less data.
2) AMD is a major cause of blindness worldwide, affecting millions of aging individuals, and neovascular AMD can cause severe vision loss without treatment.
3) Landmark clinical trials have established ranibizumab as the standard of care for neovascular AMD, demonstrating long-term vision gains and stability with both fixed and individualized dosing regimens.
The document provides an overview and summary of developments in ophthalmology in 2014. Some key points:
- The 7th Annual OIS@AAO conference had over 750 attendees from 32 states and 22 countries representing various sectors.
- The FDA approved 4 new ophthalmic drugs in 2014 including treatments for glaucoma, cataract surgery pain/miosis, and diabetic macular edema.
- Clinical trials are ongoing for several potential new treatments for wet AMD, DME, dry eye disease, uveitis, and glaucoma that could report data in 2015.
This document summarizes key aspects of sensory evaluation of squint or strabismus. It begins by describing normal binocular development and vision, including the development of binocular fusion and stereopsis in infants. It then discusses abnormal binocular vision including sensory adaptations like suppression, anomalous retinal correspondence, and eccentric fixation. Finally, it outlines several tests used to evaluate the sensory system in strabismus, including visual acuity tests, Worth four-dot test, Bagolini striated glasses, 4 prism base out test, synaptophore, and after-image tests.
Macular Degeneration - Update on clinical trial results and new treatmentspresmedaustralia
The CATT study found that ranibizumab (Lucentis) and bevacizumab (Avastin) produced similar visual acuity outcomes for wet AMD over 2 years. However, bevacizumab was less effective in reducing retinal swelling. There were also more serious systemic side effects with bevacizumab. While deaths, heart attacks and strokes were low with both drugs, CATT was not large enough to determine if there were meaningful differences in these rare but serious side effects. More research is still needed to determine longer term safety and efficacy.
This document discusses retinal breaks and retinal detachment. Some key points:
- Retinal breaks can cause retinal detachment and occur in about 6% of the population, with retinal detachment occurring in around 0.07% of people in their lifetime.
- Common causes of retinal breaks include trauma, vitreous traction, and increasing age. Symptoms may include floaters, photopsias, and vitreous hemorrhage.
- Examination involves slit lamp biomicroscopy and sometimes B-scan ultrasound or vitrectomy. Certain lesions like retinal dialysis, horseshoe tears, and operculated tears often warrant treatment to prevent retinal detachment, while smaller lesions may not require intervention
The document discusses various causes and clinical approaches to evaluating proptosis in adults. Common causes in adults include thyroid eye disease, pseudotumor, orbital cellulitis, trauma, meningioma, lymphoma, and cavernous hemangioma. A thorough history, examination, and imaging studies are needed to differentiate between causes and guide treatment.
ULTRASONOGRAPHY (USG) AND ULTRASOUND BIOMICROSCOPY(UBM)Dr. Gaurav Shukla
Ultrasonography and ultrasound biomicroscopy are important tools for diagnosing ocular and orbital abnormalities. Ultrasonography uses high frequency sound waves transmitted into the eye via a probe to image intraocular structures. A-scans display returning echoes in one dimension while B-scans create a two-dimensional image by accumulating A-scan echoes. B-scans are useful for evaluating lesions' topography, reflectivity, internal structure, and mobility. Common applications include detecting retinal detachments, vitreous opacities, intraocular tumors, and foreign bodies. Ultrasonography is valuable for screening and characterizing many ocular pathologies.
This document discusses intravitreal injections for drug delivery to the posterior segment of the eye. It begins by explaining the challenges of drug delivery due to the blood-ocular barrier and how sustained release systems and nano-particles were developed. It then provides details on the procedure of intravitreal injection, including indications, agents used, aseptic technique, complications, and anti-VEGF agents like bevacizumab, ranibizumab, pegaptanib, and aflibercept.
This document provides an outline and overview of lamellar keratoplasty techniques. It discusses the anatomy of the cornea and indications for lamellar keratoplasty such as keratoconus. Anterior lamellar keratoplasty techniques include deep anterior lamellar keratoplasty (DALK) using the big bubble technique or Melle's technique to remove the corneal stroma down to Descemet's membrane. Posterior lamellar keratoplasty techniques like Descemet's stripping endothelial keratoplasty (DSEK) are also summarized. Complications of lamellar keratoplasty procedures and advantages over penetrating keratoplasty are highlighted.
This document discusses techniques for managing a small pupil during cataract surgery. Small pupils are defined as less than 4mm in diameter and can increase risks of complications during surgery. Medications like Flomax and glaucoma medications can cause miosis preoperatively. Intracameral lidocaine and epinephrine or Omidria can help maintain pupil size during surgery. For small, floppy pupils, iris hooks, retractors, or expansion rings can be used. For small, stiff pupils, mechanical stretching techniques may work better. Proper pupil management techniques can help reduce surgical risks in patients with small pupils.
The document discusses the evaluation of strabismus. It defines strabismus and the different types such as phoria, tropia, comitant, and incomitant. It describes the history to obtain and various tests used in the examination including motor function tests like cover test, versions, and ductions, and sensory tests like Worth 4-dot and Bagolini lenses. The document provides details on the order and components of a complete ocular examination for strabismus.
The document discusses recent advances in the management of obstruction of the lacrimal drainage system. It describes the history and evolution of various surgical techniques for treating this obstruction, including external dacryocystorhinostomy (DCR), endoscopic endonasal DCR, ultrasonic endoscopic DCR, non-laser endonasal DCR, endocanalicular laser DCR, and balloon-assisted DCR. It then provides details on the surgical procedure for external DCR, including patient preparation, instrumentation, osteotomy creation, flap formation, flap anastomosis, wound closure, and post-operative management. Potential complications are also briefly mentioned.
This document discusses the diagnosis and management of superior oblique palsy. It begins by describing the anatomy and function of the superior oblique muscle. Superior oblique palsy can result in hypertropia, excyclotorsion, and esotropia that are greater in certain gazes. Causes may be congenital or acquired from trauma or vascular issues. Diagnosis involves evaluating eye movements, diplopia, and head tilt. Non-surgical treatment includes patching or prisms while surgery involves weakening the antagonist inferior oblique muscle or tucking the superior oblique tendon. The goal of treatment is to expand the field of single vision while minimizing complications.
This case study describes a child with congenital cataracts who underwent multiple surgeries and treatments over several years. By age 11, the child had developed severe vision loss with only light perception vision in the right eye and 20/200 vision in the left eye. Visual field loss progressed significantly over time. Low vision recommendations evolved from stand magnifiers and telescopes to focus on braille, audiobooks, screen reading software, and closed circuit television to help the child continue their education despite declining vision.
This document discusses fundus examination and its importance in ophthalmology. Fundus examination can detect signs of circulatory, metabolic, and neurological disorders. It is used to identify and locate retinal and optic nerve defects caused by eye disease or trauma, examine the extent of abnormalities to plan treatment, and evaluate treatment success. The document describes different methods of performing fundus examination including direct ophthalmoscopy, indirect ophthalmoscopy, and indirect slit lamp biomicroscopy. It provides examples of common fundus findings and conditions that can be assessed via this examination.
This document provides an overview of branched retinal vein occlusion (BRVO). It discusses the classification, epidemiology, risk factors, pathogenesis, signs and symptoms, diagnostic evaluation, and management of BRVO. Key points include that BRVO is the most common type of retinal vein occlusion and risk factors include hypertension, glaucoma, hyperlipidemia, and advancing age. Diagnostic testing includes fluorescein angiography and OCT to evaluate for macular edema, capillary nonperfusion, and neovascularization. Laser photocoagulation and anti-VEGF injections are common treatment approaches for complications such as macular edema.
Branched Retinal Vein Occlusion (BRVO) for undergraduate MBBS Students.
Covers the basics of Aetiology, pathophysiology, clinical features, types, associated conditions and management of BRVO.
Also encompasses salient points for PGMEE
This document discusses rhegmatogenous retinal detachment (RRD), which occurs when there is a full-thickness defect in the retina allowing fluid from the vitreous to enter the subretinal space. RRD is usually preceded by posterior vitreous detachment. The pathogenesis involves dynamic vitreoretinal traction and predisposing peripheral retinal degeneration. Common predisposing factors are lattice degeneration and retinal tears caused by vitreous traction. Management options include scleral buckling surgery, pneumatic retinopexy, and pars plana vitrectomy, with the goal of identifying and closing all retinal breaks.
This document discusses perimetry and visual field testing. It defines visual field as the area that can be seen at a given moment. There are various methods of visual field testing including kinetic and static perimetry. Automated static perimetry tests like Humphrey and Octopus are now commonly used and test the threshold light intensity that can be detected at different points in the visual field. The results are analyzed based on total deviation plots, pattern deviation plots and global indices to detect and monitor glaucomatous visual field defects. Common patterns of visual field defects seen in different conditions are also described.
A case of dense nuclear cataract has undergone phacoemulsificaton by horizontal chop technique. the pupil was small so Iris retractor was utilized. Intraocular lens was implanted.
The document discusses implantable contact lenses (ICL) for correcting high refractive errors. Key points include:
- ICL is preferred over LASIK for high myopia or thin corneas, as it has fewer risks of complications.
- ICL is made of a biocompatible collamer material and is implanted in the posterior chamber behind the iris.
- A clinical trial found nearly 60% of eyes achieved 20/20 vision and 95% achieved 20/40 vision or better after 3 years with ICL implantation.
- Complications are generally low but can include cataracts, increased eye pressure, damage to the natural lens, and other rare issues like infections. Most risks are
This document discusses idiopathic juxtafoveolar telangiectasia (IJFT), including its classification and stages. It describes IJFT types 1 and 2, with type 1 being congenital and aneurysmal and type 2 being acquired and perifoveal. Type 2 is further classified into 5 stages based on angiographic and imaging findings. The document also presents three case studies where anti-VEGF therapy with ranibizumab was used to treat neovascularization associated with types 1 and 2 IJFT, showing improvements in leakage and vision. While anti-VEGF therapy may help reduce leakage, preexisting photoreceptor damage from IJFT may limit improvements in visual acuity.
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANIAjayDudani1
1) Ranibizumab is the preferred molecule for treating neovascular AMD due to the extensive evidence from numerous clinical trials proving its long-term safety and efficacy compared to alternatives like biosimilars which have less data.
2) AMD is a major cause of blindness worldwide, affecting millions of aging individuals, and neovascular AMD can cause severe vision loss without treatment.
3) Landmark clinical trials have established ranibizumab as the standard of care for neovascular AMD, demonstrating long-term vision gains and stability with both fixed and individualized dosing regimens.
The document provides an overview and summary of developments in ophthalmology in 2014. Some key points:
- The 7th Annual OIS@AAO conference had over 750 attendees from 32 states and 22 countries representing various sectors.
- The FDA approved 4 new ophthalmic drugs in 2014 including treatments for glaucoma, cataract surgery pain/miosis, and diabetic macular edema.
- Clinical trials are ongoing for several potential new treatments for wet AMD, DME, dry eye disease, uveitis, and glaucoma that could report data in 2015.
Central Retinal Vein OcclUsIon (CRUISE) Study - Cruise trialLaxmi Eye Institute
Ranibizumab injections led to improved visual acuity and resolution of macular edema compared to sham injections in patients with central retinal vein occlusion. At 6 months, patients receiving 0.3 mg or 0.5 mg ranibizumab were twice as likely to have a visual acuity of 20/40 or better compared to the sham group. Ranibizumab also significantly reduced central foveal thickness within 7 days, suggesting retinal edema in CRVO is primarily VEGF-mediated. While ranibizumab was effective, longer term studies are needed to determine optimal duration of treatment and benefits in less severe cases.
This study analyzed reports of adverse drug reactions (ADRs) affecting the eye that were reported in Switzerland from 1991 to 2016. Of the over 80,000 ADR reports in total, 3.5% (2,793 reports) were related to eye disorders. Drugs acting on the nervous system were most commonly associated with eye ADRs. Older patients experienced more serious eye ADRs and were prescribed more medications on average. Anti-vascular endothelial growth factor drugs, used to treat eye diseases, accounted for 99 reports of eye ADRs since 2000, with retinal hemorrhage, blindness, and uveitis being more commonly reported for aflibercept. This study highlights the need for continued monitoring of
Breaking the barriers in the management of neovascular AMDAjayDudani1
The document summarizes key details from two phase 3 clinical trials called HAWK and HARRIER that compared the anti-VEGF drug brolucizumab to aflibercept for treating neovascular age-related macular degeneration (nAMD). The trials involved over 1700 patients across multiple international sites. Patients were randomly assigned to receive either brolucizumab 3mg or 6mg, or aflibercept 2mg. The primary endpoint was change in vision from baseline at week 48, with assessments continuing through week 96. Brolucizumab demonstrated non-inferiority to aflibercept and an ability to be dosed as infrequently as every 12 weeks after the initial
Vascular endothelial growth factors promote neovascularization and break the blood-retinal barrier. Anti-vascular endothelial growth factor (anti-VEGF) therapies block VEGF's actions, decreasing abnormal new blood vessel formation and retinal leakage/swelling. This stabilizes vision and may improve it. Bevacizumab, ranibizumab, and aflibercept are examples of anti-VEGF drugs used intravitreally to treat wet age-related macular degeneration, diabetic retinopathy, retinal vein occlusion and other conditions. While effective, anti-VEGF therapies require frequent injections and monitoring for side effects like increased intraocular pressure.
Vision Medicines is developing two drug candidates, VM100 and VM200, to treat retinal diseases with high unmet medical need and large market opportunities. VM100 is in Phase 2/3 development for geographic atrophy and intermediate AMD, with a combined $20B market. VM200 is in preclinical development for Stargardt disease, an orphan indication with no approved therapies and a $6B market opportunity. Both drugs address the underlying disease mechanisms and have demonstrated preclinical efficacy in preserving retinal structure and function. Vision Medicines aims to develop these assets and consolidate the fragmented ophthalmology space, which has fewer products per company than other therapeutic areas.
Anti-VEGF drugs like ranibizumab and bevacizumab have revolutionized the treatment of eye diseases like age-related macular degeneration by inhibiting abnormal blood vessel growth, but their long-term safety and high cost remain uncertain, and studies question whether less frequent dosing regimens could achieve similar results with fewer injections. A new anti-VEGF drug, aflibercept, has been approved and may require fewer injections than ranibizumab, but its long-term efficacy and safety also need further evaluation.
1. VEGF is a growth factor that promotes abnormal blood vessel growth in the retina and is responsible for many retinal diseases. Anti-VEGF drugs like ranibizumab (Lucentis), bevacizumab (Avastin), and pegaptanib (Macugen) block VEGF to inhibit this blood vessel growth and treat retinal diseases.
2. While ranibizumab, Avastin, and pegaptanib are all anti-VEGF drugs, they differ in their structure and dosing. Ranibizumab and Avastin are antibodies while pegaptanib is a nucleic acid. Avastin costs $45 per dose while ranibizumab costs over $1500.
3. Clinical trials found ranib
Gene therapy with recombinant adeno-associated vectors was tested for neovascular age-related macular degeneration in a phase 1 clinical trial. Nine patients were enrolled and randomly assigned to receive either a low dose (3 patients) or high dose (3 patients) of rAAV.sFLT-1 gene therapy, or no treatment (2 control patients). The gene therapy was delivered via subretinal injection and was found to be safe and well tolerated with no drug-related adverse events. Patients receiving gene therapy required fewer rescue injections of ranibizumab over the one-year follow-up period compared to control patients, suggesting rAAV.sFLT-1 may provide long-term treatment effects for
VEGF is a growth factor that promotes abnormal blood vessel growth in the retina and causes vision loss. Anti-VEGF drugs like ranibizumab (Lucentis), bevacizumab (Avastin), and pegaptanib (Macugen) work by blocking VEGF and stopping this blood vessel growth. Ranibizumab was designed specifically for eye injections and has a short half-life, while bevacizumab was designed for cancer but is also used "off-label" in the eye. Clinical trials found that both drugs are effective in treating wet AMD, diabetic retinopathy, and other retinal diseases, but ranibizumab may have a slightly lower risk of rare side effects due to its shorter exposure in
Clinical and Pharmacoeconomic analysis was extensivley done on Eylea for its placement on a hypothetical health plans formulary for Macular Degeneration. Information was presented to a panel of pharmacy professionals in managed care and industry
Eylea (aflibercept) is an effective treatment for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) that requires fewer injections than alternatives like ranibizumab. It has a stronger binding affinity to VEGF than ranibizumab and bevacizumab, and can suppress VEGF for longer. Clinical trials showed patients receiving Eylea achieved vision gains and needed on average 5 fewer injections over 2 years compared to monthly ranibizumab. Eylea is also highly effective for occult CNV, PED, and has shown vision gains maintained over 2 years in PCV with more than 30% of patients achieving complete polyp
The development & approval of Novoeight, a case studyAllen Che
The FDA approved Novoeight, a recombinant Factor VIII treatment for hemophilia A, in October 2013 based on positive results from clinical trials. Novoeight was found to effectively control and prevent bleeding episodes in adults and children with hemophilia A. The approval process involved reviewing manufacturing, clinical data, and inspections to ensure safety and efficacy. This approval expands treatment options for hemophilia A patients and represents continued innovation in the development of safer recombinant clotting factor therapies.
This document discusses NT-501, a potential drug for treating geographic atrophy due to age-related macular degeneration. It begins by explaining that NT-501 is ciliary neurotrophic factor delivered to the retina via encapsulated cell technology implants. Studies found that NT-501 resulted in retinal thickness increases and visual acuity stabilization in patients. The conclusion is that NT-501 delivered by encapsulated cells appears to slow vision loss in geographic atrophy, especially for patients with better baseline vision.
This document describes a clinical trial protocol to evaluate the efficacy and safety of Loteprednol Etabonate Ophthalmic Suspension 1% w/v compared to Loteprednol Etabonate Ophthalmic Suspension 0.5% w/v for the treatment of post-operative inflammatory conditions of the eye. The randomized, double-blind, parallel group trial will enroll 206 subjects to receive either the 1% or 0.5% suspension twice daily for 18 days. The primary endpoint is the proportion of subjects with complete resolution of anterior chamber cells at day 8. Secondary endpoints include resolution of anterior chamber flare and pain scores. The trial eligibility criteria, design, procedures, and assessments are provided in
Presentation from OIS@ASCRS 2016
James Brandt, MD, Principal Investigator
Video Presentation:
https://www.youtube.com/watch?v=jvIozhPMSQ8&list=PL1dmdBNnPTZJBhQxPOp0vdNg3s3wtN2yw&index=30
This document provides an overview of pharmacovigilance and International Council for Harmonisation (ICH) guidelines related to pharmacovigilance. It defines key terms like adverse events, adverse drug reactions, and serious adverse events. It also summarizes several ICH guidelines that provide recommendations for clinical safety data management, expedited reporting, periodic benefit-risk evaluation reports, and pharmacovigilance planning over the lifecycle of a drug. The document outlines guidelines for good clinical practice, clinical trials in special populations like pediatrics, and evaluation of new drugs like antihypertensives and those affecting the QT interval.
Biosimilars IN RETINAL DISORDERS -DR AJAY DUDANIAjayDudani1
This document discusses the treatment of retinal conditions with a focus on anti-VEGF therapies. It provides a history of the development of anti-VEGF treatments from the discovery of VEGF in the 1980s and 1990s to the approval of ranibizumab and aflibercept in the 2000s. It then discusses the evolution of ranibizumab and the evidence from clinical trials supporting its use. Finally, it addresses biosimilars that are attempting to enter the anti-VEGF market and highlights some of the differences between biosimilars and innovator biologics.
This document discusses the treatment of retinal conditions with a focus on anti-VEGF therapies. It provides a history of the development of anti-VEGF treatments from the discovery of VEGF in the 1980s and 1990s to the approval of ranibizumab and aflibercept in the 2000s. It then discusses the evolution of ranibizumab and the evidence from clinical trials supporting its use. Finally, it addresses biosimilars that are attempting to enter the anti-VEGF market and highlights some of the differences between biosimilars and innovator biologics.
Similar to Intraocular safety OF ANTIVEGF INJECTIONS IN THE EYE (20)
The document contains 6 sections describing different clinical cases involving retinal imaging with AngioPlex. Each section includes AngioPlex maps of the superficial retina, deeper retina, avascular retina, and in some cases choroid, along with B-scan flow images. The cases include wet AMD with CNV, DR, BRVO, and MacTel and provide AngioPlex imaging data for patients ranging in age from 48-76 years old, examining both right and left eyes.
Post-operative endophthalmitis (POE) is an inflammatory response in the eye following surgery that can lead to vision loss. It is most commonly caused by bacteria entering through surgical wounds. POE presents with pain, redness, decreased vision and occurs usually 1-7 days after surgery. Treatment involves intravenous and intravitreal antibiotics based on culture and vitrectomy in severe cases. Proper pre-operative cleaning and use of prophylactic antibiotics can help prevent POE. A case of retained intraocular foreign body following a work injury is also discussed, demonstrating the importance of safety equipment and need for thorough examination and removal of any objects in such cases.
Recent advances in OCT technology were discussed. New features of Cirrus HD-OCT include enhanced imaging capabilities like OCT angiography, improved anterior segment imaging, swept source technology, and enhanced visualization tools. Clinical cases were also presented to demonstrate the utility of these new technologies in evaluating and managing various retinal diseases.
The document shares the author's personal story of losing his father during medical school, completing his training, and eventually opening his own eye centers in Mumbai. It then offers guidance for physicians starting private practices, including the benefits of being your own boss, building a patient base through strategic location and care, finding a niche, and prioritizing patient satisfaction over profits. The author believes reports of private practice being dead are exaggerated and that it can allow a good work-life balance if done correctly.
Oct guided diagnosis and treatment of pathologic myopic cnvm -AJAY DUDANIAjayDudani1
This document discusses the advantages of optical coherence tomography (OCT) over fluorescein angiography (FFA) for evaluating myopic choroidal neovascularization (CNVM). OCT allows visualization of retinal layers and pathological changes in greater detail without the invasiveness and side effects of FFA. Studies have shown that OCT is better than FFA at diagnosing myopic CNVM, and that restoration of the external limiting membrane (ELM) on OCT following treatment correlates with improved visual outcomes. The document presents two case studies of patients with myopic CNVM who were treated using anti-VEGF injections guided by SD-OCT findings without performing FFA.
Comparison resight AND OTHER_fundus_viewing SYSTEMS-DR AJAY DUDANIAjayDudani1
This document contains a series of slides comparing the RESIGHT Fundus Viewing System from Carl Zeiss Meditec AG to other fundus viewing systems such as those from Oculus, Topcon, and Volk. The RESIGHT System is highlighted as having excellent Zeiss optics, constant distance to the patient's cornea during focusing, a lens turret for fast access to a second lens, and efficient workflow when used with the motorized Invertertube and MediLive Trio Eye video cameras. It is also noted as having a stable working height and only requiring the lens holder and lenses to be sterilized.
This document discusses diabetic macular edema (DME), its causes and prevalence, current treatments, and evidence for the use of ranibizumab (Lucentis) in the treatment of DME. Some key points:
- DME is the main cause of central vision loss in diabetic retinopathy and can affect 10-25% of diabetics depending on type of diabetes and insulin use.
- Current treatments include controlling blood sugar, blood pressure, lipids as well as laser photocoagulation and pharmacologic therapies like steroids and anti-VEGF drugs.
- Studies like RESOLVE, READ-2 and DRCR.net trials showed ranibizumab led to significant gains in
Debate lattice degenertion to laser OR NOT-AJAY DUDANIAjayDudani1
This document discusses retinal complications that can occur after LASIK surgery, particularly retinal detachment. It notes that while the incidence of retinal detachment after LASIK is low (around 0.05-0.08%), it is more common in highly myopic eyes. Lattice degeneration and atrophic retinal holes are identified as risk factors. The document debates whether prophylactic treatment of asymptomatic retinal lesions before LASIK is necessary or effective, as studies have found similar rates of retinal detachment in treated and untreated groups. Overall it emphasizes the need for counseling highly myopic patients with lattice degeneration undergoing LASIK, but cautions against overtreating asymptomatic lesions.
The document discusses common eye problems in children, including refractive errors, amblyopia, strabismus, blocked tear ducts, conjunctivitis, and computer vision syndrome. It recommends regular vision screenings for newborns, infants, and preschoolers. Warning signs of various conditions are provided. Causes, symptoms, and treatment approaches are described for several pediatric eye disorders.
1) The document discusses various treatment options for central retinal vein occlusion (CRVO) including anti-VEGF drugs such as ranibizumab, aflibercept, and bevacizumab as well as steroid implants like dexamethasone and triamcinolone.
2) Clinical trials showed anti-VEGF drugs provided significant vision gains compared to observation alone, while results were mixed for other options like photocoagulation and steroids.
3) Long-term follow up data demonstrated the need for ongoing treatment to maintain vision gains in CRVO patients, with some achieving resolution of edema and excellent outcomes.
Central serous chorioretinopathy DR AJAY DUDANIAjayDudani1
Central Serous Chorioretinopathy (CSCR) is characterized by serous retinal detachment in the macular region. Stress and corticosteroids are known risk factors for CSCR. This study evaluated 100 CSCR patients treated with anxiolytics and/or antidepressants to reduce stress levels. Rapid resolution of retinal detachment occurred in 90% of acute cases treated with anxiolytics alone or combined with antidepressants within 2-3 weeks. Chronic or recurrent CSCR cases showed improvement but 2 cases required additional half-fluence photodynamic therapy. The results demonstrate effectiveness of reducing stress hormones with medications for treating CSCR.
Anti vegf switch-DR AJAY I DUDANI-MUMBAI RETINA CENTREAjayDudani1
This document discusses the case of an 84-year-old male patient with wet age-related macular degeneration (AMD) in both eyes who was initially treated with photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) injections in his left eye, resulting in a macular scar and vision loss. For his right eye (RE), he received 27 injections of ranibizumab (Lucentis) over 11 years with decreasing efficacy over time. In September 2014, the patient was switched to aflibercept (Eylea), with his RE remaining dry since his second aflibercept injection in January 2015. The document reviews studies on switching patients
The CATT trial compared the efficacy and safety of monthly ranibizumab, monthly bevacizumab, PRN ranibizumab, and PRN bevacizumab for wet AMD over 1 year. At 1 year, both monthly bevacizumab and PRN bevacizumab were found to be non-inferior to their ranibizumab counterparts in mean change in visual acuity from baseline. PRN bevacizumab resulted in more injections on average compared to PRN ranibizumab. Ranibizumab monthly resulted in a greater mean decrease in total retinal thickness compared to other groups. There were no significant differences in serious systemic adverse events between drugs, though bevacizumab patients had
This document summarizes a study on the outcomes of scleral buckling surgery for rhegmatogenous retinal detachment. The study included 50 patients who underwent scleral buckling with cryotherapy, encirclage, and a localized buckle. Immediately after surgery, the retina was reattached in 45 patients, for a success rate of 90%. Complications included recurrent detachment in 5 patients who required vitrectomy, and epiretinal membrane or macular pucker in 2 patients. The document argues that while scleral buckling is less commonly performed now than vitrectomy, it remains an effective technique for uncomplicated retinal detachment, especially in younger patients, with advantages of lower cost
This document discusses diabetic macular edema (DME), its causes and prevalence, current treatments, and evidence for the use of ranibizumab (Lucentis) in the treatment of DME. Some key points:
- DME is the main cause of central vision loss in diabetic retinopathy and can affect 10-25% of diabetics depending on type of diabetes and insulin use.
- Current treatments include controlling blood sugar, blood pressure, lipids, and ocular treatments like laser photocoagulation and pharmacologic therapies like steroids and anti-VEGF drugs.
- Studies like RESOLVE, READ-2, and RESTORE showed ranibizumab significantly improved visual
Central serous chorioretinopathy DR AJAY DUDANIAjayDudani1
Central Serous Chorioretinopathy and Anxiolytics and Antidepressants
This document summarizes a study on the effectiveness of oral anxiolytics and antidepressants in treating central serous chorioretinopathy (CSCR) in patients with type A personalities and anxiety disorders. The study found that acute CSCR cases resolved rapidly within 2-3 weeks in 90% of patients treated with anxiolytics alone or combined with antidepressants. Vision improved in all acute cases. Chronic CSCR cases showed slower improvement, with most reaching 6/12 vision or better. The hypothesis is that anxiety and stress increase corticosteroid levels, disrupting the blood-retinal barrier and choroidal circulation,
This document presents several case studies of patients with various retinal conditions treated with Ozurdex (dexamethasone intravitreal implant). The cases include patients with diabetic macular edema, central retinal vein occlusion, pseudophakic cystoid macular edema, Vogt-Koyanagi-Harada syndrome, serpigenous choroiditis, and lamellar macular hole. Therapies involved Ozurdex either alone or in combination with anti-VEGF agents, steroids, and/or laser photocoagulation. Ozurdex provided effective control of macular edema and inflammation in many of these difficult cases.
PREOP ANTIBIOTICS FOR CATARACT SURGERY DR AJAY DUDANIAjayDudani1
The document discusses strategies to prevent post-operative endophthalmitis following cataract surgery. It finds that pre-operative povidone-iodine and topical antibiotics can significantly reduce conjunctival bacterial flora. Intracameral antibiotics during surgery, such as cefuroxime, also significantly lower the risk of endophthalmitis. Fourth generation fluoroquinolones like moxifloxacin and gatifloxacin are more potent than earlier generations against gram-positive bacteria. Subconjunctival antibiotics administered with surgery may halve the risk of post-operative endophthalmitis. Comprehensive pre, during and post-operative antibiotic protocols are important to minimize this potentially devastating
This document summarizes the management of retinopathy of prematurity (ROP) with ranibizumab (Lucentis) and laser photocoagulation. It discusses the pathogenesis, classification, and risk factors of ROP. Current treatment modalities include laser photocoagulation, anti-VEGF therapies like ranibizumab and bevacizumab, and cryotherapy. The document also describes a case study where 20 eyes with zone-1 stage 3+ ROP were successfully treated with intravitreal injections of ranibizumab followed by laser photocoagulation, with no complications. Ranibizumab was chosen due to its smaller size, shorter half-life, and reduced risk of systemic effects compared
Avastin for one &aII; everyone DR AJAY DUDANIAjayDudani1
This document discusses the use of Avastin (bevacizumab) versus Lucentis (ranibizumab) for treating retinal conditions. It argues that Avastin is more affordable and effective based on trial results. It acknowledges Avastin was developed for cancer but cites evidence it works well for wet AMD and other retinal diseases. The document advocates treating patients with Avastin instead of Lucentis to save costs while still providing good vision outcomes.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
DECLARATION OF HELSINKI - History and principlesanaghabharat01
This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
How to Control Your Asthma Tips by gokuldas hospital.Gokuldas Hospital
Respiratory issues like asthma are the most sensitive issue that is affecting millions worldwide. It hampers the daily activities leaving the body tired and breathless.
The key to a good grip on asthma is proper knowledge and management strategies. Understanding the patient-specific symptoms and carving out an effective treatment likewise is the best way to keep asthma under control.
Know the difference between Endodontics and Orthodontics.Gokuldas Hospital
Your smile is beautiful.
Let’s be honest. Maintaining that beautiful smile is not an easy task. It is more than brushing and flossing. Sometimes, you might encounter dental issues that need special dental care. These issues can range anywhere from misalignment of the jaw to pain in the root of teeth.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
Lecture 6 -- Memory 2015.pptlearning occurs when a stimulus (unconditioned st...AyushGadhvi1
learning occurs when a stimulus (unconditioned stimulus) eliciting a response (unconditioned response) • is paired with another stimulus (conditioned stimulus)
2. Disclaimer
• Use of these slides is permitted only for the purpose of scientific and educational presentations.
• While every reasonable effort has been made to ensure accuracy of content, it is the responsibility of the
practitioner, relying on experience and knowledge of the patient, to determine the best treatment for each
individual patient. Bayer shall not be responsible or in any way liable for the continued accuracy &/or veracity of the
information or for any errors, omissions or inaccuracies or for any injury and/or damage to persons or property
arising from relying on the information contained in the presentation or otherwise.
• The data contained herein does not reflect the views or opinion of Bayer for use of product in indications in which it
is not approved.
• Bayer shall not be responsible/ liable for miscommunication of this data if they are altered/ tampered in any
manner.
• Opinions expressed do not necessarily reflect the views of Bayer. Medical knowledge is constantly changing, so
standard safety precautions must be followed.
• For use of Registered Medical Practitioners only
• Eylea (Aflibercept) is approved in nAMD/PCV indications in India.
3. The ASRS has recently released several member updates on IOI and occlusive retinal vasculitis
following brolucizumab administration. The information contained herein provides an update on
relevant intraocular safety information following aflibercept injection and provides context for the
ASRS communications.
Hot topics deck: Intraocular safety of anti-VEGF agents
ASRS, American Society of Retina Specialists; IOI, intraocular inflammation; VEGF, vascular endothelial growth factor.
4. Aflibercept has a well-established safety profile across RCTs
supported by real-world pharmacovigilance monitoring
.
AE, adverse event; IOI, intraocular inflammation; RAO, retinal artery occlusion; RCT, randomized controlled trial.
1. Bayer. Data on file; April 2020. 2. Bayer AG. EYLEA – summary of product characteristics; May 2020. 3. Kitchens JW et al. Ophthalmology 2016; 123 (7): 1511–1520.
Aflibercept has over 4.8 million patient-years of exposure and more than 34 million vials have been sold since
its launch.1 It has a well-established ocular and systemic safety profile across clinical trials in multiple indications,
and real-world pharmacovigilance monitoring demonstrates that it is well tolerated in clinical practice.1–3
The post-marketing reporting rate of ocular (retinal) vasculitis after aflibercept is 0.00002%
(7 cases overall in more than 34 million vials sold)*,1
To date, there are no new safety concerns regarding the development of retinal vasculitis and/or
retinal vascular occlusion that may result in severe vision loss following intravitreal aflibercept injection
The rate of IOI with aflibercept in routine clinical practice has remained low at 0.012%
(1.2 cases per 10,000 vials sold)1
The rate of endophthalmitis / non-infectious endophthalmitis with aflibercept in routine clinical practice
has remained low at 0.007% (0.7 cases in 10,000 vials sold)1
5. In a comprehensive review of 8 RCTs across 4 indications, rates of ocular and
systemic AEs were low with aflibercept and similar to the control arm
*The uncontrolled trials CLEAR-IT 2 and VIEW 1 extension were included in order to maximize the aflibercept exposure in the study.
AE, adverse event; APTC, Antiplatelet Trialists’ Collaboration; ATE, arterial thromboembolic event; BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; DME, diabetic macular edema;
IOI, intraocular inflammation; ME, macular edema; MI, myocardial infarction; nAMD, neovascular age-related macular degeneration; RCT, randomized controlled trial; RR, rate ratio; SAE, serious adverse event.
Kitchens JW et al. Ophthalmology 2016; 123 (7): 1511–1520.
• Kitchens et al. performed a comprehensive
review of the rates of ocular and non-ocular
AEs with aflibercept and its respective
comparators (predominantly ranibizumab,
but also laser and sham)
• Data were pooled from eight RCTs (Phase II
and Phase III) and two uncontrolled trials*
o Review included 4,203 patients with follow-up
ranging from <6 months to >5 years
• Rates of ocular and non-ocular AEs across
indications either do not differ between
aflibercept and its comparator, or favor
aflibercept over its comparator
0 1 2 3 4 5
IOI
Endophthalmitis
Wound-healing complications
Hypertension
SAE
All APTC-defined ATEs
Non-fatal MI
Non-fatal stroke
Vascular death
Death
Rate ratios of intravitreal aflibercept injection vs. control for AEs across
nAMD, ME after CRVO, ME after BRVO, and DME
Favors treatment Favors control
RR
6. IOI is a well-known but rare ocular AE that has historically been observed at
comparably low rates across clinical trials with all anti-VEGF agents
*Included the following terms: anterior chamber cell, anterior chamber flare, aqueous fibrin, endophthalmitis, eye infection, eye inflammation, hypopyon, iridocyclitis, iritis, non-infectious endophthalmitis, uveitis, vitreal cells, and
vitritis. AE, adverse event; IOI, intraocular inflammation; VEGF, vascular endothelial growth factor.
Bayer. Data on file; Integrated analysis – Core RMP update for IOI.
In VIEW 1 and VIEW 2, the rates of any IOI-related AE in the study eye were low over 96 weeks:
0.41% per injection
(40 cases in 9,805 injections)
Ranibizumab 0.5 mg
0.28% per injection
(74 cases in 26,366 injections)
Aflibercept arms pooled
7. Endophthalmitis is a well-known but rare ocular AE that has historically been
observed at comparably low rates across clinical trials with all anti-VEGF agents
AE, adverse event; q4, every 4 weeks; q8, every 8 weeks, after 3 initial monthly doses; VEGF, vascular endothelial growth factor.
Schmidt-Erfurth U et al. Ophthalmology 2014; 121 (1): 193–201.
In VIEW 1 and VIEW 2, the rates of endophthalmitis in the study eye were low over 96 weeks:
VIEW 1/2 (n=595)
0.8%
Ranibizumab 0.5 mg Aflibercept 2 mg q8
VIEW 1/2 (n=610)
0%
Aflibercept 2 mg q4
VIEW 1/2 (n=613)
0.7%
8. Overall rates of serious ocular AEs, including endophthalmitis, were
low in Phase III RCTs of aflibercept across retinal disease indications
.
*2 mg q8 after 3 initial monthly doses. †2 mg q8 after 5 initial monthly doses. AE, adverse event; CRVO, central retinal vein occlusion; DME, diabetic macular edema; nAMD, neovascular age-related macular degeneration;
PRN, pro re nata (as needed); q4, every 4 weeks; q8, every 8 weeks; RCT, randomized controlled trial.
1. Schmidt-Erfurth U et al. Ophthalmology 2014; 121 (1): 193–201. 2. Kaiser PK et al. Ophthalmol Retina 2017; 1 (4): 304–313. 3. Heier JS et al. Ophthalmology 2016; 123 (11): 2376–2385.
4. Brown DM et al. Am J Ophthalmol 2013; 155 (3): 429–437. 5. Heier JS et al. Ophthalmology 2014; 121 (7): 1414–1420. 6. Ogura Y et al. Am J Ophthalmol 2014; 158 (5): 1032–1038.
Trial – indication
Follow-up period for ocular SAE reporting
Treatment (regimen) Endophthalmitis, %
VIEW 1 and VIEW 2 – nAMD1
Follow-up to Week 96
Ranibizumab (0.5 mg q4, then modified quarterly dosing from Week 52) 0.8 (n=5/595)
Aflibercept (2 mg q8*, 2 mg q4, or 0.5 mg q4, then modified quarterly dosing from Week 52) 0.3 (n=5/1,824)
VIEW 1 extension – nAMD2
Follow-up from Week 96 to Week 212
Aflibercept (2 mg, modified quarterly dosing) 0.9 (n=3/323)
VIVID and VISTA – DME3
Follow-up to Week 148
Laser 0 (n=0/287)
Aflibercept (2 mg q8† or 2 mg q4) 0.5 (n=3/578)
COPERNICUS – CRVO4,5
Follow-up to Week 24
Sham 0 (n=0/74)
Aflibercept (2 mg q4) 0.9 (n=1/114)
Follow-up from Week 24 to Week 100
Weeks 0–24: sham;
Weeks 24–100: aflibercept (2 mg PRN)
0 (n=0/60)
Weeks 0–24: aflibercept (2 mg q4);
Weeks 24–100: aflibercept (2 mg PRN)
0 (n=0/110)
GALILEO – CRVO6
Follow-up to Week 76
Weeks 0–48: sham;
Weeks 52–76: aflibercept (2 mg PRN)
0 (n=0/68)
Weeks 0–20: aflibercept (2 mg q4);
Weeks 24–76: aflibercept (2 mg PRN)
0 (n=0/104)
Follow-up from Week 52 to Week 76
Weeks 0–48: sham;
Weeks 52–76: aflibercept (2 mg PRN)
0 (n=0/52)
Weeks 0–20: aflibercept (2 mg q4);
Weeks 24–76: aflibercept (2 mg PRN)
0 (n=0/91)
9. What information is provided in the recent ASRS communications
relating to brolucizumab and what are the current recommendations?
Hot topics deck: Intraocular safety of anti-VEGF agents
ASRS, American Society of Retina Specialists; VEGF, vascular endothelial growth factor.
10. Summary of recent events, including ASRS member alerts, an ASRS special report,
and several case reports relating to IOI and RAO / occlusive retinal vasculitis
ASRS, American Society of Retina Specialists; FDA, Food and Drug Administration; IOI, intraocular inflammation; nAMD, neovascular age-related macular degeneration; RAO, retinal artery occlusion; SRC, Safety Review Committee.
1. Novartis Pharmaceuticals Corp. Beovu – prescribing information; October 2019. 2. ASRS member communication; January 2020. 3. ASRS member communication; February 2020. 4. Safety of Beovu® (brolucizumab). Available at: https://www.brolucizumab.info. Accessed
June 2020. 5. ASRS member communication; March 2020. 6. Haug SJ et al. Am J Ophthalmol Case Rep 2020; 18: 100680. 7. Jain A et al. Am J Ophthalmol Case Rep 2020; 18: 100687. 8. Baumal CR et al. Ophthalmology 2020; Epub ahead of print (DOI: 10.1016/
j.ophtha.2020.04.017). 9. ASRS Special Report: Occlusive retinal vasculitis following intravitreal brolucizumab: An ASRS Research and Safety in Therapeutics (ReST) Committee Report; Spring 2020. 10. Safety of Beovu® (brolucizumab). Available at:
https://www.brolucizumab.info/. Accessed June 2020. 11. Rosenfeld PJ et al. Am J Ophthalmol 2020; doi: 10.1016/j.ajo.2020.05.012. 12. Retinal Physician. Editorial Calls for Halting Use of Beovu. Available at: https://www.retinalphysician.com/issues/2020/june-2020/editorial-
calls-for-halting-use-of-Beovu. Accessed June 2020. 13. ASRS member communication; June 2020. 14. Novartis. US FDA approves updated Novartis Beovu® label, to include additional safety information. Available at: https://www.novartis.com/news/media-releases/us-fda-
approves-updated-novartis-beovu-label-include-additional-safety-information. Accessed June 2020.
ASRS Special Report
Comprehensive report with updated information on cases
and numbers. Overall, 26 eyes from 25 patients were reported as
having retinal vasculitis, of which 22 eyes were designated occlusive.9
Oct
2019
Jan
2020
Mar
2020
Feb
2020
Apr
2020
Brolucizumab approved
for the treatment of
nAMD in the USA.1
ASRS member communication
Alert released to raise awareness of the
incidence of potential occlusive retinal
vasculitis with brolucizumab. Overall, 14
cases of retinal vasculitis were reported,
of which 11 were designated occlusive.3
First published case reports
• Retinal arterial occlusive vasculitis following
intravitreal brolucizumab administration.6
• Severe vision loss secondary to retinal
arteriolar occlusions after multiple intravitreal
brolucizumab administrations.7
• Retinal vasculitis and intraocular inflammation
after intravitreal injection of brolucizumab.8
Novartis confirms safety
signal with brolucizumab10
Launch of www.brolucizumab.info
Website providing updates on the safety
profile of brolucizumab.4
ASRS member communication
The ASRS warned physicians that it had begun
to receive physician reports of IOI following
administration of brolucizumab.2
ASRS member communication
Update released providing details on reports of vasculopathy,
including occlusive retinal vasculitis, with brolucizumab.5
May
2020
Jun
2020
Editorial article calls for
halting use of brolucizumab11
Two US clinicians provided their
perspective on the response of the
medical community to reports of IOI
following brolucizumab. This was
followed by a response from Novartis on
June 1 in Retinal Physician.12
ASRS member communication
Update released detailing the findings of the
Novartis-commissioned SRC review of safety data
from the Phase III HAWK and HARRIER trials.13
FDA approved updated
brolucizumab label
that includes additional
safety information14
11. HAWK and HARRIER: Patients receiving brolucizumab experienced
higher rates of serious ocular AEs compared with aflibercept
*Results focus on the safety database from HAWK and HARRIER, with supportive safety data provided from OSPREY, OWL, SHRIKE, and SEE. A brolucizumab 3 mg treatment group was included in HAWK only. †Uveitis = preferred
terms; uveitis, anterior chamber inflammation, and vitritis. A subject with multiple occurrences of a SAE for a preferred term is counted only once for that preferred term. ‡No explanation was provided as to why uveitis was reported
twice in this summary of SAEs. SAEs occurring in 1 subject in any treatment group: cataract subcapsular, dry AMD, macular hole, anterior chamber inflammation, blindness, cataract, cataract – traumatic, dacryocystitis, retinal artery
embolism, retinal depigmentation, retinopathy proliferative, vitritis.
AE, adverse events; AMD, age-related macular degeneration; FDA, Food and Drug Administration; EMA, European Medicines Agency IOI, intraocular inflammation; SAE, serious adverse events; VA, visual acuity.
1. FDA drug approval package: BEOVU (brolucizumab-dbII); Clinical review(s). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000MedR.pdf. Accessed June 2020.
2. Beovu – European public assessment report. Available at: https://www.ema.europa.eu/en/documents/assessment-report/beovu-epar-public-assessment-report_en.pdf. Accessed June 2020.
Serious ocular AEs occurring in ≥1 subjects in any treatment group
HAWK Pooled HAWK and HARRIER*
Brolucizumab 3 mg
(n=358)
Brolucizumab 6 mg
(n=730)
Aflibercept 2 mg
(n=729)
Subjects with ≥1 SAE, n (%) 6 (1.7) 25 (3.4) 11 (1.5)
AEs occurring in ≥1 subjects in any
treatment group, n (%)
Uveitis† 1 (0.3) 7 (1.0) 0
Endophthalmitis 3 (0.8) 4 (0.5) 1 (0.1)
Retinal artery occlusion 3 (0.8) 0 1 (0.1)
Uveitis‡ 1 (0.3) 5 (0.7) 0
VA reduced 0 2 (0.3) 3 (0.4)
Retinal detachment 1 (0.3) 2 (0.3) 2 (0.3)
Retinal artery thrombosis 0 2 (0.3) 0
Retinal pigment epithelial tear 0 2 (0.3) 0
Retinal tear 0 2 (0.3) 1 (0.1)
Both the FDA and EMA acknowledged more patients in the pooled brolucizumab
6 mg groups experienced serious ocular AEs than the pooled aflibercept groups1,2
12. • Aflibercept has a well-established safety profile across RCTs supported by real-world pharmacovigilance monitoring.
• The rate of IOI with aflibercept in routine clinical practice has remained low at 0.012% (1.2 cases per 10,000 vials
sold)
• The rate of endophthalmitis / non-infectious endophthalmitis with aflibercept in routine clinical practice
has remained low at 0.007% (0.7 cases in 10,000 vials sold)
• The post-marketing reporting rate of ocular (retinal) vasculitis after aflibercept is 0.00002%
(7 cases overall in more than 34 million vials sold)
• In a comprehensive review of 8 RCTs across 4 indications, rates of ocular and systemic AEs were low with aflibercept
and similar to the control arm.
• HAWK and HARRIER: Both the FDA and EMA acknowledged more patients in the pooled Brolucizumab
6 mg groups experienced serious ocular AEs than the pooled Aflibercept groups.
• Rates of IOI were 5-fold higher among patients who received Brolucizumab 6 mg compared with patients who
received aflibercept (4.4% [95%CI: 2.30–7.08] vs 0.8% [95%CI 0.14–1.63], respectively)
• The EMA noted a signal for increased IOI risk with Brolucizumab compared with aflibercept, with a risk difference of
3.6% (95% CI: 1.08–6.53) between the treatment groups in favour of aflibercept.
• The ASRS has recently released several member updates on IOI and occlusive retinal vasculitis following Brolucizumab
administration
Summary
13. HAWK and HARRIER: Patients receiving brolucizumab experienced numerically higher
rates of IOI, including more cases of endophthalmitis, than those receiving aflibercept
AEs with a start date on or after the date of first study drug administration are counted. AEs with a start date on or after the start date of treatment with an alternative anti-VEGF are not included. *Results focus on the safety database
from HAWK and HARRIER, with supportive safety data provided from OSPREY, OWL, SHRIKE, and SEE. A brolucizumab 3 mg treatment group was included in HAWK only. †Preferred term: retinopathy hypertensive. ‡Preferred term:
contusion. AE, adverse event; CI, confidence interval; EMA, European Medicines Agency; FDA, Food and Drug Administration; IOI, intraocular inflammation; IOP, intraocular pressure; VEGF, vascular endothelial growth factor.
1. FDA drug approval package: BEOVU (brolucizumab-dbII); Clinical review(s). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000MedR.pdf. Accessed June 2020.
2. Beovu – European public assessment report. Available at: https://www.ema.europa.eu/en/documents/assessment-report/beovu-epar-public-assessment-report_en.pdf. Accessed June 2020.
Preferred term, n (%) [eyes]
HAWK Pooled HAWK and HARRIER*
Brolucizumab 3 mg
(n=358)
Brolucizumab 6 mg
(n=730)
Aflibercept 2 mg
(n=729)
Subjects with ≥1 AE 59 (16.5) [96] 105 (14.4) [161] 86 (11.8) [110]
IOI 16 (4.5) [25] 32 (4.4) [44] 6 (0.8) [10]
Endophthalmitis 4 (1.1) [4] 5 (0.7) [5] 1 (0.1) [1]
IOP increased 18 (5.0) [33] 28 (3.8) [4.1] 33 (4.5) [44]
Hypersensitivity 11 (3.1) [11] 18 (2.5) [22] 19 (2.6) [20]
Retinal pigment epithelial tear 5 (1.4) [6] 20 (2.7) [20] 8 (1.1) [9]
Glaucoma 5 (1.4) [5] 4 (0.5) [4] 9 (1.2) [9]
Arterial thromboembolic events 4 (1.1) [5] 9 (1.2) [9] 3 (0.4) [3]
Retinal arterial occlusive events 4 (1.1) [5] 6 (0.8) [6] 1 (0.1) [1]
Venous thromboembolic events 3 (0.8) [3] 0 0
Vitreous hemorrhage 1 (0.3) [1] 1 (0.1) [1] 3 (0.4) [3]
Hypertension† 1 (0.3) [1] 0 0
Non-ocular hemorrhage‡ 0 0 2 (0.3) [2]
Traumatic cataract 0 1 (0.1) [1] 0
Ocular AEs in the study eye potentially related to intravitreal anti-VEGF1
Both the FDA and the EMA highlighted that the rate of IOI was higher in the pooled
brolucizumab 6 mg groups compared with the pooled aflibercept groups at Week 961,2
• Rates of IOI were 5-fold higher among patients who received brolucizumab 6 mg compared with patients
who received aflibercept (4.4% [95%CI: 2.30–7.08] vs 0.8% [95%CI 0.14–1.63], respectively)1,2
• The EMA noted a signal for increased IOI risk with brolucizumab compared with aflibercept, with a risk
difference of 3.6% (95% CI: 1.08–6.53) between the treatment groups in favor of aflibercept2
14. January 22, 2020: The ASRS issued a member alert highlighting
first reports of IOI following use of brolucizumab in clinical practice
AE, adverse event; ASRS, American Society of Retina Specialists; FDA, Food and Drug Administration; IOI, intraocular inflammation; ReST, Research and Safety in Therapeutics.
ASRS member communication; January 2020.
The ASRS encouraged practitioners to report
all drug- and device-related AEs and reminded
members that administration of brolucizumab and
aflibercept is contraindicated in the setting of
active IOI (drug-related or otherwise), according to
their FDA labels.
[Brolucizumab] update for ASRS members
“The ASRS ReST Committee has begun to receive physician reports
of intraocular inflammation following administration of Beovu.
In the pivotal Phase III trials, inflammation was noted in up to
4% of Beovu patients as indicated on the FDA label.
The ASRS encourages practitioners to report all drug- and
device-related adverse events. Particularly in the setting of a newly
approved dug or device, such reports are critical in defining our
real-world experienced through analysis of the aggregate of
collected reports. We remind members that administration of Beovu
and Eylea is contraindicated in the setting of active intraocular
inflammation (drug-related or otherwise), according to their FDA
labels.”
15. February 23, 2020: The ASRS issued a member alert highlighting
cases of occlusive vasculitis following brolucizumab administration
ASRS, American Society of Retina Specialists; FDA, Food and Drug Administration; IOI, intraocular inflammation; VEGF, vascular endothelial growth factor.
ASRS member communication; February 2020.
• An ASRS member update was released to
raise awareness of the incidence of potential
occlusive retinal vasculitis within the
ophthalmology community and to encourage
close monitoring for IOI following brolucizumab
treatment
• In addition to cases of mild to moderate IOI,
these reports included 14 cases of vasculitis,
of which 11 were designated as occlusive
retinal vasculitis
• The ASRS urged clinicians to carefully inspect
the eye for any IOI immediately prior to
injection of brolucizumab and to defer anti-
VEGF administration when any concerning
signs of inflammation are present
[Brolucizumab] update for ASRS members
“Since FDA approval of Beovu on [October 7, 2019], the ASRS has received reports
of intraocular inflammation following Beovu administration. In addition to cases
of mild–moderate intraocular inflammation, these reports have included 14 cases
of vasculitis, of which 11 were designated as occlusive retinal vasculitis by the
reporting provider. Novartis estimates that approximately 46,000 injections have
been administered to date in the US. The etiology of these events is unclear. Long-
term outcomes and optimal treatment strategies are not defined at this time…
In the setting of Beovu-associated inflammation, the ASRS encourages close follow
up and appropriate imaging, as some cases of occlusive vasculitis may initially be
subtle or present in a delayed fashion.
Current, and future, informed consent should appropriately discuss and
document potential risks.
We urge vigilance and reporting of any adverse treatment-related events,
regardless of agent, by all practitioners. The ASRS will continue to track these
events and update the retina community as further information
becomes available.”
16. March 30, 2020: The ASRS issued a member update detailing post-approval
cases of occlusive retinal vasculitis reported with brolucizumab1
AMD, age-related macular degeneration; ASRS, American Society of Retina Specialists; FDA, Food and Drug Administration; ReST, Research and Safety in Therapeutics.
1. ASRS member communication; March 2020. 2. ASRS Special Report. Occlusive retinal vasculitis following intravitreal brolucizumab: An ASRS Research and Safety in Therapeutics (ReST) Committee Report; Spring 2020.
3. ASRS member communication; February 2020.
• Key findings from a safety analysis by the
ASRS ReST Committee were reported in this
update and later highlighted in an ASRS Special
Report (April 7, 2020)2
• This update included reports of vasculopathy
including occlusive vasculitis following
brolucizumab from 25 eyes of 24 patients, an
increase on the 14 cases report in an earlier
member update (February 23, 2020)1–3
• The ASRS notified its members that Novartis has
appointed an independent Safety Review
Committee (SRC) to review inflammation-related
safety events in the post-marketing setting as
well as in the HAWK and HARRIER trials1
[Brolucizumab] update for ASRS members1
“Since the October 7, 2019 FDA approval of Beovu for treatment of neovascular
AMD (with permanent J-code effective on 1/1/2020), the ASRS Research and
Safety in Therapeutics (ReST) Committee has received reports of vasculopathy
including occlusive vasculitis following intravitreal injection of the drug.
From these reports, the ASRS has reviewed detailed clinical data from
25 eyes (of 24 patients) including imaging from 23 eyes…
…The ASRS will continue to follow these cases. Additionally, Novartis has
appointed an independent Safety Review Committee to review these events both
in the post-marketing setting as well as in HAWK/HARRIER. This committee
consists of both academic and private practice members, including uveitis and
imaging specialists, from around the world, and we expect that this committee
will present their findings to the retina community separately.
The ASRS will continue to keep the retina community updated with available
information and asks physicians to report any Beovu-related adverse events to
the ASRS, FDA, and Novartis. As always, the ASRS encourages active vigilance
and reporting of all drug- and device-related adverse events.”
17. • The ASRS published a Special Report detailing post-approval cases of retinal vasculitis reported
with brolucizumab
o Data from 26 eyes of 25 patients with retinal vasculitis after receiving brolucizumab were collected:
April 7, 2020: The ASRS ReST Committee concluded that intravitreal brolucizumab injection
appears to be associated with retinochoroidal vasculopathy (including occlusive vasculitis)
AE, adverse event; ASRS, American Society of Retina Specialists; ETDRS, Early Treatment Diabetic Retinopathy Study; IOI, intraocular inflammation; ReST, Research and Safety in Therapeutics; VA, visual acuity;
VEGF, vascular endothelial growth factor.
ASRS Special Report. Occlusive retinal vasculitis following intravitreal brolucizumab: An ASRS Research and Safety in Therapeutics (ReST) Committee Report; Spring 2020.
• No eyes had a history of anti-VEGF associated inflammation,
and only 1 patient had a history of iritis
• 22 of 26 eyes (85%) with retinal vasculitis were reported as
having occlusive vasculitis
• Overall, a mean vision loss of approximately 37 ETDRS letters
(between 6 and 7 lines) from baseline was recorded at the
most recent follow-up visit
• 88% of reported cases occurred in women
• All AEs arose after 1 (11 eyes, 44%), 2 (11 eyes, 44%), or
3 (4 eyes, 12%) brolucizumab injections, though it is unlikely
that a meaningful number of patients received more than
3 injections by the time of this analysis
• Mean time to presentation was 25.5 days (range 3–63 days)
from the most recent brolucizumab injection
VA parameter Snellen (approx. ETDRS letters)
All eyes (N=26)
Mean VA at baseline 20/45 (67.5)
Mean VA at most recent brolucizumab injection 20/52 (64.5)
Mean VA at AE onset 20/151 (41)
Mean worst VA 20/397 (20)
Mean VA at most recent follow-up 20/243 (31)
Eyes with >60 days of follow-up (n=8)
Mean VA at baseline 20/52 (64.5)
Mean VA at AE onset 20/145 (42)
Mean worst VA 20/512 (14.5)
Mean VA at most recent follow-up 20/214 (33.5)
18. Of the 8 eyes that were re-treated with a different anti-VEGF agent after diagnosis of an AE related to brolucizumab:1
The ASRS Special Report included information on 8 eyes that were re-treated with
a different anti-VEGF agent after diagnosis of an AE related to brolucizumab
AE, adverse event; ASRS, American Society of Retina Specialists; ReST, Research and Safety in Therapeutics; VEGF, vascular endothelial growth factor.
1. ASRS Special Report. Occlusive retinal vasculitis following intravitreal brolucizumab: An ASRS Research and Safety in Therapeutics (ReST) Committee Report; Spring 2020. 2. Bayer AG. EYLEA – summary of product characteristics;
May 2020. 3. Novartis Pharmaceuticals Corp. Beovu – prescribing information; October 2019. 4. Novartis Pharmaceuticals Corp. Lucentis – summary of product characteristics; January 2020.
• Overall, 4 of these eyes received aflibercept once inflammation had
resolved, and there was no recurrence of inflammation in those eyes
• In another 2 eyes, there was persistent posterior-only inflammation
at the time of retreatment with aflibercept, but there was no
worsening of inflammation after aflibercept injection
• In the last 2 eyes, onset of occlusive vasculitis was noted to follow
injection of anti-VEGF medication (one received aflibercept and the
other received ranibizumab) in the setting of pre-existing, active
brolucizumab-associated inflammation
If considering switching a patient experiencing brolucizumab-associated inflammation back to aflibercept, it is important
to note that intravitreal administration of any anti-VEGF agent is contraindicated in patients with active inflammation.2–4
Anti-VEGF agents should not be administered while a patient is presenting with signs of an ongoing inflammation.
19. Several case reports of patients who experienced RAO and severe vision loss
after intravitreal brolucizumab injections have now been published1–3
RAO, retinal artery occlusion; VA, visual acuity; VEGF, vascular endothelial growth factor.
1. Haug SJ et al. Am J Ophthalmol Case Rep 2020; 18: 100680. 2. Jain A et al. Am J Ophthalmol Case Rep 2020; 18: 100687. 3. Baumal C et al. Ophthalmology 2020: doi: https://doi.org/10.1016/ j.ophtha.2020.04.017.
A total of 18 eyes were included
across all published case reports, all of
which were previously treated with
other anti-VEGF agents, including
aflibercept, without any inflammatory
response prior to switching to
brolucizumab. After switching to
brolucizumab, several patients
experienced life-impacting vision loss,
and their VA did not return to baseline
(i.e. before the switch) after cessation
of brolucizumab treatment.3
20. Novartis concluded there is a confirmed safety signal of rare AEs of “retinal vasculitis and/or retinal
vascular occlusion that may result in severe vision loss” after intravitreal brolucizumab injection
*Event rates are discrete; there is no duplication between categories. †Includes reports of retinal artery occlusion, retinal artery thrombosis, retinal artery embolism, retinal ischemia, arterial occlusive disease, and retinal vascular
occlusion. AE, adverse event; IOI, intraocular inflammation; SAE, serious adverse event.
1. ASRS Special Report: Occlusive retinal vasculitis following intravitreal brolucizumab: An ASRS Research and Safety in Therapeutics (ReST) Committee Report; Spring 2020.
2. Safety of Beovu® (brolucizumab). Available at: https://www.brolucizumab.info. Accessed June 2020.
It is estimated that 70,000 brolucizumab vials have been used post-marketing in 37,000 unique patients.1
AE* Post-marketing AE rates
Total of three events of interest 6.99 per 10,000 injections
Retinal vasculitis 1.69 per 10,000 injections
Retinal vascular occlusion
†
1.57 per 10,000 injections
Retinal vasculitis and retinal vascular occlusion* 3.73 per 10,000 injections
The SRC also conducted an unmasked review of a subset of imaging data from HAWK and HARRIER and indicated that
they saw some of the same AEs in the trials. They found that these events occurred on a spectrum ranging from IOI to
vasculitis to occlusive events that sometimes resulted in vision loss. The SRC continues to review safety data from the
HAWK and HARRIER trials and is expected to publish its independent review in the coming months.2
Current safety data from the brolucizumab information website (as of May 8, 2020)2
Brolucizumab
21. Post-marketing reporting rates of “retinal vasculitis and/or retinal
vascular occlusion” with aflibercept remain low since its launch
*Event rates are discrete; there is no duplication between categories. †Includes reports of retinal vasculitis, ocular vasculitis, hemorrhagic vasculitis (upon review = ocular occurrence). ‡Includes reports of RAO, retinal artery
embolism, retinal artery stenosis, retinal artery thrombosis, retinal artery spasm, retinal ischemia, retinal vascular occlusion, retinal vascular thrombosis. §Includes one case where aflibercept was injected in active IOI/vitritis
following brolucizumab and the patient developed hemorrhagic vasculitis and RAO, and one case reported as occlusive vasculitis that was deemed appropriate for the combination category.
AE, adverse event; IOI, intraocular inflammation; RAO, retinal artery occlusion.
Bayer. Data on file; April 2020.
As of March 31, 2020 more than 34 million aflibercept vials had been sold globally.
AE* Post-marketing AE rates
Total of three events of interest 0.03 per 10,000 sold vials
Retinal vasculitis
†
0.001 per 10,000 sold vials
Retinal vascular occlusion
‡
0.03 per 10,000 sold vials
Retinal vasculitis and retinal vascular occlusion
§
0.0006 per 10,000 sold vials
Safety data for aflibercept information website (case data as of April 30; exposure as of March 31, 2020)
Aflibercept
22. Across clinical trials and real-world pharmacovigilance monitoring,
retinal vasculitis has not been a safety signal with aflibercept
*Includes one case where aflibercept was injected in active IOI/vitritis following brolucizumab and developed hemorrhagic vasculitis and RAO. This patient had previously received 40 aflibercept injections and was switched because
of residual SRF, but then had vitritis at the next visit and was switched back to aflibercept immediately.
IOI, intraocular inflammation; RAO, retinal artery occlusion; SRF, subretinal fluid; VEGF, vascular endothelial growth factor.
1. Bayer. Data on file; January 2020. 2. Bayer. Data on file; April 2020. 3. Bayer AG. EYLEA – summary of product characteristics; May 2020. 4. Novartis Pharmaceuticals Corp. Beovu – prescribing information; October 2019.
5. Novartis Pharmaceuticals Corp. Lucentis – summary of product characteristics; January 2020.
None of the reported cases of retinal vasculitis were
deemed as occlusive across all Phase III trials of aflibercept.1
Post-marketing cases of vasculitis as of April 30, 20202
Ocular (retinal) vasculitis* 0.002 per 10,000 vials sold
Systemic vasculitis 0.0003 per 10,000 vials sold
Any vasculitis 0.002 per 10,000 vials sold
The post-marketing reporting rate of ocular (retinal) vasculitis after
aflibercept is 0.00002% (7 cases overall in 34 million vials sold).
One of these cases is a patient switched to aflibercept in the setting of
active inflammation / vitritis following brolucizumab administration.2
If considering switching patients back to aflibercept, it is important to
remember that aflibercept (or any anti-VEGF agent) is contraindicated
in patients with active inflammation and should not be administered
while a patient is presenting with signs of an ongoing inflammation.3–5
Rate of retinal vasculitis across pivotal
Phase III clinical trials (N=3,236)1
Rate of retinal vasculitis 0.06% (n=2)
Aflibercept
23. In May 2020, an editorial article provided the perspective of two US clinicians on the
response of the medical community to reports of IOI following brolucizumab
AE, adverse event; AMD, age-related macular degeneration; FDA, Food and Drug Administration; IOI, intraocular inflammation; nAMD, neovascular age-related macular degeneration.
1. Rosenfeld PJ et al. Am J Ophthalmol 2020; doi: 10.1016/j.ajo.2020.05.012.
2. Retinal Physician. Editorial Calls for Halting Use of Beovu. Available at: https://www.retinalphysician.com/issues/2020/june-2020/editorial-calls-for-halting-use-of-Beovu. Accessed June 2020.
• The authors praised the fast response of the ophthalmic community
in identifying cases of inflammation following brolucizumab injection
and reporting them to the appropriate authorities1
• While investigations into the causes of inflammation-related AEs
with brolucizumab are ongoing, the authors concluded that use of
brolucizumab is unwarranted since other agents are available for the
treatment of nAMD1
o Notably, they recommended that brolucizumab injections should be
stopped until further investigations are concluded and remedies
implemented, and that this should be made official by the relevant
ophthalmological societies and the FDA1
On June 1, Novartis issued a response to the editorial:
“…While we respect individual perspectives, we believe [brolucizumab]
continues to represent an important treatment option, addressing unmet needs
for patients with wet AMD, with an overall favorable benefit-risk profile.”2
24. Novartis has issued guidance for physicians around IOI-related AEs with brolucizumab
and managing patients with these events after intravitreal injection
AE, adverse event; IOI, intraocular inflammation; VA, visual acuity; VEGF, vascular endothelial growth factor.
Safety of Beovu® (brolucizumab). Available at: https://www.brolucizumab.info/. Accessed June 2020.
• Post-marketing reports of IOI-related AEs suggest that these events can occur as early as the first or second
injection of brolucizumab, with patients reporting changes in vision, such as significant increase in floaters or
blurry vision, within 1–2 weeks of treatment
• As such, Novartis provided general guidance for physicians on the www.brolucizumab.info website as follows:
• Before injecting look for signs of IOI; this may involve
examination by slit lamp or posterior segment imaging
• If active IOI is present, you must not perform an intraocular
injection and should treat the IOI according to medical practice
• Instruct your patients to contact you immediately if they notice
any changes in VA or any signs of inflammation, such as eye pain,
floaters, discomfort, or ocular hyperemia
• As a reminder, all anti-VEGF agents are contraindicated in patients
with ocular or periocular infections, active IOI, or known
hypersensitivity to any of the excipients
25. June 4, 2020: The ASRS issued a member update detailing the findings of the
Novartis-commissioned SRC review of safety data from HAWK and HARRIER
ASRS, American Society of Retina Specialists; IOI, intraocular inflammation; ReST, Research and Safety in Therapeutics; SRC, Safety Review Committee; VEGF, vascular endothelial growth factor.
ASRS member communication; June 2020.
• The occurrence of IOI in association with retinal vasculitis and
retinal vascular occlusion is a new safety signal that appears
to be specific to brolucizumab.
• 23 treatment-naive patients (2.1%) treated with
brolucizumab developed IOI with concomitant retinal
vasculitis and vascular occlusion, while just 1 patient (0.1%)
treated with aflibercept was found to have “probable” IOI
with retinal vasculitis and retinal vascular occlusion.
• It is difficult to predict when inflammation events will occur
after brolucizumab injection. In cases where a patient has
tolerated brolucizumab treatment for a period of time, they
may still be at risk of experiencing inflammation events after
brolucizumab injection.
• The ASRS ReST Committee did not provide a conclusive
statement on the risk–benefit profile of brolucizumab,
instead recommending that the risk–benefit profile should be
determined by the treating physician on a case-by-case basis.
[Brolucizumab] update for ASRS members
• “Post-marketing reports have highlighted the occurrence of IOI in association
with retinal vasculitis and retinal vascular occlusion with brolucizumab, which
differs from the common experience with other approved anti-VEGF agents.”
• “IOI of any form was identified in 4.6% (50/1,088) of study patients.
Of those, 36 subjects had concomitant retinal vasculitis for an overall rate of
3.3% (36/1,088). Of the 36 subjects with IOI and vasculitis, 23 subjects had
concomitant vascular occlusion for an overall rate of 2.1% (23/1,088).”
• “…although the SRC identified that the majority of inflammation events
presented within the first 6 months of brolucizumab initiation (74%, 37/50),
some events presented between 12–18 months (12%, 6/50).”
• “The ReST Committee believes that this risk–benefit assessment at the
individual patient level is best determined by the judgment of the
treating provider.”
26. June 10, 2020: The FDA approved updates to the US Prescribing Information for
brolucizumab to include the new safety signal under ‘Warnings and Precautions’1,2
AE, adverse event; FDA, Food and Drug Administration; IOI, intraocular inflammation.
1. Novartis. US FDA approves updated Novartis Beovu® label, to include additional safety information. Available at: https://www.novartis.com/news/media-releases/us-fda-approves-updated-novartis-beovu-label-include-additional-
safety-information. Accessed June 2020. 2. Novartis Pharmaceuticals Corp. Beovu – prescribing information; June 2020.
The update to the US label includes characterization of
retinal vasculitis and retinal vascular occlusion as part of
the spectrum of IOI-related AEs observed in HAWK and
HARRIER, and includes the addition of a sub-section
dedicated to retinal vasculitis and/or retinal vascular
occlusion under ‘Warnings and Precautions’ (Section 5
of the US Prescribing Information).1
“Retinal vasculitis and/or retinal vascular occlusion,
typically in the presence of intraocular inflammation,
have been reported with the use of [brolucizumab].
Patients should be instructed to report any
change in vision without delay.” 2
27. Aflibercept has a well-established safety profile across RCTs
supported by real-world pharmacovigilance monitoring
*Includes one case where aflibercept was injected in active IOI/vitritis following brolucizumab and the patient developed hemorrhagic vasculitis and RAO. This patient had previously received 40 aflibercept injections and was
switched because of residual SRF, but then had vitritis at the next visit and was switched back to aflibercept immediately.
AE, adverse event; IOI, intraocular inflammation; RAO, retinal artery occlusion; RCT, randomized controlled trial.
1. Bayer. Data on file; April 2020. 2. Bayer AG. EYLEA – summary of product characteristics; May 2020. 3. Kitchens JW et al. Ophthalmology 2016; 123 (7): 1511–1520.
Aflibercept has over 4.8 million patient-years of exposure and more than 34 million vials have been sold since
its launch.1 It has a well-established ocular and systemic safety profile across clinical trials in multiple indications,
and real-world pharmacovigilance monitoring demonstrates that it is well tolerated in clinical practice.1–3
The post-marketing reporting rate of ocular (retinal) vasculitis after aflibercept is 0.00002%
(7 cases overall in more than 34 million vials sold)*,1
To date, there are no new safety concerns regarding the development of retinal vasculitis and/or
retinal vascular occlusion that may result in severe vision loss following intravitreal aflibercept injection
The rate of IOI with aflibercept in routine clinical practice has remained low at 0.012%
(1.2 cases per 10,000 vials sold)1
The rate of endophthalmitis / non-infectious endophthalmitis with aflibercept in routine clinical practice
has remained low at 0.007% (0.7 cases in 10,000 vials sold)1
28. Levels of ADAs increased with exposure to brolucizumab –
why have the EMA and FDA highlighted this finding?
Hot topics deck: Intraocular safety of anti-VEGF agents
ADA, anti-drug-antibodies; EMA, European medicines agency; FDA, Food and Drug Administration; VEGF, vascular endothelial growth factor.
29. HAWK and HARRIER: Anti-drug antibodies (ADAs) increased with
brolucizumab exposure
ADA, anti-drug antibodies; FDA, Food and Drug Administration; nAb, neutralizing antibodies; SPC, summary of product characteristics.
1. FDA drug approval package: BEOVU (brolucizumab-dbII); Clinical pharmacology review(s). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000ClinPharmR.pdf. Accessed June 2020.
2. Regeneron Pharmaceuticals. EYLEA – prescribing information; December 2011. 3. Bayer AG. EYLEA – summary of product characteristics; May 2020.
HAWK
(n=360)
HARRIER
(n=369)
Total
(N=729)
Baseline ADA+ 128 (36%) 193 (52%) 321 (44%)
≥1 sample ADA+ 241 (67%) 281 (76%) 522 (72%)
Baseline nAb+ 15 (4%) 105 (29%) 120 (17%)
≥1 sample nAb+ 81 (23%) 151 (41%) 232 (32%)
Neutralizing antibodies were detected in 23–41%
patients receiving brolucizumab 6 mg
Immunogenicity status of patients receiving brolucizumab 6 mg in the safety population1
ADAs were detected in
the pre-treatment serum
sample of up to half of
treatment-naive patients
After initiation of dosing,
the presence of
ADAs increased
In the US prescribing information for aflibercept, pre-treatment incidence of ADAs to
aflibercept was 1–3%. After dosing with aflibercept for 24–100 weeks, ADAs did not increase.2
The EU SPC for aflibercept does not include reference to incidence of ADAs.3
Brolucizumab
Aflibercept
30. HAWK
(n=360)
HARRIER
(n=369)
Total
(N=729)
Baseline ADA+ 128 (36%) 193 (52%) 321 (44%)
≥1 sample ADA+ 241 (67%) 281 (76%) 522 (72%)
Baseline nAb+ 15 (4%) 105 (29%) 120 (17%)
≥1 sample nAb+ 81 (23%) 151 (41%) 232 (32%)
Immunogenicity status of patients receiving brolucizumab 6 mg in the safety population1
HAWK and HARRIER: Anti-drug antibodies (ADAs) increased with
brolucizumab exposure
ADA, anti-drug antibodies; EMA, European Medicines Agency; FDA, Food and Drug Administration; IOI, intraocular inflammation; nAb, neutralizing antibodies.
1. FDA drug approval package: BEOVU (brolucizumab-dbII); Clinical pharmacology review(s). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000ClinPharmR.pdf. Accessed June 2020.
2. Beovu – European public assessment report. Available at: https://www.ema.europa.eu/en/documents/assessment-report/beovu-epar-public-assessment-report_en.pdf. Accessed June 2020. 3. Novartis Pharmaceuticals
Corp. Beovu – prescribing information; October 2019,
• The EMA highlighted the potential for an immune response in patients treated with brolucizumab; among
patients with treatment-emergent ADAs, a higher number of IOI adverse reactions were observed2
• The FDA also highlighted that IOI was observed in 6% of patients with treatment-emergent antibodies
(and in 2% patients without positive antibodies)3
• Both the EMA and FDA noted that the clinical relevance of the impact of ADAs on safety remains unclear2,3
Brolucizumab
31. Summary: Intraocular safety of anti-VEGF agents
ADA, anti-drug antibody; AE, adverse event; CI, confidence interval; EMA, European Medicines Agency; FDA, Food and Drug Administration; IOI, intraocular inflammation; SRC, safety review committee; VEGF, vascular endothelial growth factor.
1. FDA drug approval package: BEOVU (brolucizumab-dbII); Clinical review(s). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000MedR.pdf. Accessed June 2020. 2. Beovu – European public assessment report. Available
at: https://www.ema.europa.eu/en/documents/assessment-report/beovu-epar-public-assessment-report_en.pdf. Accessed June 2020. 3. Novartis Pharmaceuticals Corp. Beovu – prescribing information; October 2019. 4. Bayer. Data on file; April 2020. 5. Bayer
AG. EYLEA – summary of product characteristics; May 2020.6. Kitchens JW et al. Ophthalmology 2016; 123 (7): 1511–1520. 7. ASRS Special Report: Occlusive retinal vasculitis following intravitreal brolucizumab: An ASRS Research and Safety in Therapeutics
(ReST) Committee Report; Spring 2020. 8. Safety of Beovu® (brolucizumab). Available at: https://www.brolucizumab.info/. Accessed June 2020. 9. Novartis Pharmaceuticals Corp. Lucentis – summary of product characteristics; January 2020.
10. FDA drug approval package: BEOVU (brolucizumab-dbII); Clinical pharmacology review(s). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000ClinPharmR.pdf. Accessed June 2020. 11. Regeneron Pharmaceuticals.
EYLEA – prescribing information; December 2011.
The rate of serious ocular AEs was numerically higher with brolucizumab than with aflibercept in HAWK and HARRIER, and
the rate of IOI with brolucizumab was 5-fold that with aflibercept. The EMA noted a signal for increased IOI risk with
brolucizumab, with a risk difference of 3.6% (95% CI: 1.08–6.53) between the treatment groups in favor of aflibercept.1–3
• Aflibercept has over 4.8 million patient-years of exposure and more than 34 million vials have been sold since its launch.3 It has a
well-established ocular and systemic safety profile across clinical trials in multiple indications, and real-world pharmacovigilance
monitoring demonstrates that it is well tolerated in clinical practice.4–6
Novartis and an independent external SRC concluded that there is a confirmed safety signal of rare AEs of “retinal vasculitis
and/or retinal vascular occlusion that may result in severe vision loss” after intravitreal brolucizumab injection.7,8
• To date, there are no new safety concerns regarding the development of retinal vasculitis and/or retinal vascular occlusion that may result
in severe vision loss following intravitreal aflibercept injection.
• If considering switching patients back to aflibercept, it is important to remember that intravitreal administration of aflibercept (or any
anti-VEGF agent) is contraindicated in patients with active inflammation. Therefore, anti-VEGF agents should not be administered while
a patient is presenting with signs of an ongoing inflammation.3,5,9
The brolucizumab US label highlights that ADAs increased with brolucizumab exposure, and that IOI was observed in 6% of
patients with treatment-emergent antibodies in HAWK and HARRIER.10
• In contrast, the US prescribing information aflibercept states that after dosing with aflibercept for 24–100 weeks, ADAs did not increase;
however, the clinical relevance of the impact of ADAs on vision and safety remains unclear.10,11