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 summarizes several studies and clinical trials related to the treatment of diabetic retinopathy and diabetic macular edema. It discusses the Diabetic Retinopathy Study (DRS) and Early Treatment Diabetic Retinopathy Study (ETDRS) which established laser photocoagulation as the standard treatment for proliferative diabetic retinopathy and diabetic macular edema. It also summarizes the Diabetic Retinopathy Clinical Research Network (DRCR.Net) which conducted several clinical trials comparing treatments for diabetic macular edema such as anti-VEGF injections and laser photocoagulation. The document provides high-level overviews of many landmark studies that helped advance the treatment of diabetic eye disease.
This document discusses retinopathy of prematurity (ROP), including:
1. A case of ROP is presented with fundus examination findings over multiple dates. Laser treatment was performed on the left eye.
2. The classification of ROP is explained according to the International Classification of ROP including zone, severity, extent, plus disease, and pre-plus disease. Threshold disease requiring treatment is defined.
3. Screening, examination, and treatment guidelines for ROP are outlined including who to screen, timing of exams, examination procedure and documentation, and treatment indications. Cryotherapy and laser ablation are discussed as standard treatments.
This document provides information on anti-VEGF drugs used in ophthalmology. It discusses the role of VEGF in various eye diseases and conditions. It summarizes the properties, mechanisms of action, administration, and safety profiles of major anti-VEGF drugs including bevacizumab, pegaptanib, and ranibizumab which are used to treat wet age-related macular degeneration, diabetic retinopathy, and other retinal diseases by inhibiting abnormal blood vessel growth and leakage caused by VEGF.
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 provides an overview of proliferative vitreoretinopathy (PVR). It defines PVR as a fibrotic wound healing response involving proliferation of cells that can cause retinal traction and detachment. The pathophysiology involves epithelial-mesenchymal transition of retinal pigment epithelium cells and proliferation of glial cells, which secrete extracellular matrix proteins. Growth factors and cytokines promote proliferation and contraction of fibrocellular membranes. Risk factors include retinal detachment, inflammation, and previous vitreoretinal surgery. Early diagnosis and timely surgery aiming to relieve traction and reattach the retina are important for treatment.
Surgery for proliferative diabetic retinopathyAmit Srivastava
- Eckardt forceps
- Horizontal scissors
- Vertical scissors
Surgeon:
- Membrane pick
- Knobbed spatula
- Scissors
- Gently lift the edge of the membrane with
forceps and cut it with scissors
- Dissect the membrane from the retina using
scissors or pick
- Dissect in a circumferential manner from the
periphery towards the center
- Apply endodiathermy to bleeding vessels
- Remove all membranes
- Use scleral depression to flatten the globe and
facilitate dissection
- Use bimanual technique for difficult membranes
- Apply PRP after membrane removal
This document discusses transpupillary thermotherapy (TTT), a technique that uses low-level heat delivered through the pupil to treat conditions like choroidal neovascularization (CNV), choroidal melanoma, and retinoblastoma. TTT works by inducing tumor necrosis or occlusion of neovascular vessels via localized hyperthermia above 42°C. The document outlines the laser parameters used to treat CNV via TTT, noting that a pilot study found 19% of patients experienced improved vision, 56% had no change, and 25% had declining vision, while 94% saw reduced exudation. TTT is currently being used and studied as a treatment for several ocular diseases.
This document discusses non-penetrating glaucoma surgery techniques that facilitate the drainage of aqueous humor through the trabecular meshwork and Schlemm's canal without opening the anterior chamber. It describes several procedures including deep sclerectomy, viscocanalostomy, canaloplasty, ab-externo trabeculectomy, and laser trabecular ablation. The goal is to bypass the highest resistance point to outflow in the juxtacanalicular meshwork. Advantages include lower risks of complications like hypotony compared to penetrating surgeries. Indications and contraindications are provided for various non-penetrating glaucoma procedures.
This document summarizes several studies and clinical trials related to the treatment of diabetic retinopathy and diabetic macular edema. It discusses the Diabetic Retinopathy Study (DRS) and Early Treatment Diabetic Retinopathy Study (ETDRS) which established laser photocoagulation as the standard treatment for proliferative diabetic retinopathy and diabetic macular edema. It also summarizes the Diabetic Retinopathy Clinical Research Network (DRCR.Net) which conducted several clinical trials comparing treatments for diabetic macular edema such as anti-VEGF injections and laser photocoagulation. The document provides high-level overviews of many landmark studies that helped advance the treatment of diabetic eye disease.
This document discusses retinopathy of prematurity (ROP), including:
1. A case of ROP is presented with fundus examination findings over multiple dates. Laser treatment was performed on the left eye.
2. The classification of ROP is explained according to the International Classification of ROP including zone, severity, extent, plus disease, and pre-plus disease. Threshold disease requiring treatment is defined.
3. Screening, examination, and treatment guidelines for ROP are outlined including who to screen, timing of exams, examination procedure and documentation, and treatment indications. Cryotherapy and laser ablation are discussed as standard treatments.
This document provides information on anti-VEGF drugs used in ophthalmology. It discusses the role of VEGF in various eye diseases and conditions. It summarizes the properties, mechanisms of action, administration, and safety profiles of major anti-VEGF drugs including bevacizumab, pegaptanib, and ranibizumab which are used to treat wet age-related macular degeneration, diabetic retinopathy, and other retinal diseases by inhibiting abnormal blood vessel growth and leakage caused by VEGF.
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 provides an overview of proliferative vitreoretinopathy (PVR). It defines PVR as a fibrotic wound healing response involving proliferation of cells that can cause retinal traction and detachment. The pathophysiology involves epithelial-mesenchymal transition of retinal pigment epithelium cells and proliferation of glial cells, which secrete extracellular matrix proteins. Growth factors and cytokines promote proliferation and contraction of fibrocellular membranes. Risk factors include retinal detachment, inflammation, and previous vitreoretinal surgery. Early diagnosis and timely surgery aiming to relieve traction and reattach the retina are important for treatment.
Surgery for proliferative diabetic retinopathyAmit Srivastava
- Eckardt forceps
- Horizontal scissors
- Vertical scissors
Surgeon:
- Membrane pick
- Knobbed spatula
- Scissors
- Gently lift the edge of the membrane with
forceps and cut it with scissors
- Dissect the membrane from the retina using
scissors or pick
- Dissect in a circumferential manner from the
periphery towards the center
- Apply endodiathermy to bleeding vessels
- Remove all membranes
- Use scleral depression to flatten the globe and
facilitate dissection
- Use bimanual technique for difficult membranes
- Apply PRP after membrane removal
This document discusses transpupillary thermotherapy (TTT), a technique that uses low-level heat delivered through the pupil to treat conditions like choroidal neovascularization (CNV), choroidal melanoma, and retinoblastoma. TTT works by inducing tumor necrosis or occlusion of neovascular vessels via localized hyperthermia above 42°C. The document outlines the laser parameters used to treat CNV via TTT, noting that a pilot study found 19% of patients experienced improved vision, 56% had no change, and 25% had declining vision, while 94% saw reduced exudation. TTT is currently being used and studied as a treatment for several ocular diseases.
This document discusses non-penetrating glaucoma surgery techniques that facilitate the drainage of aqueous humor through the trabecular meshwork and Schlemm's canal without opening the anterior chamber. It describes several procedures including deep sclerectomy, viscocanalostomy, canaloplasty, ab-externo trabeculectomy, and laser trabecular ablation. The goal is to bypass the highest resistance point to outflow in the juxtacanalicular meshwork. Advantages include lower risks of complications like hypotony compared to penetrating surgeries. Indications and contraindications are provided for various non-penetrating glaucoma procedures.
The document summarizes guidelines and recommendations for screening, diagnosing, and treating retinopathy of prematurity (ROP). ROP is a leading cause of childhood blindness that affects premature infants. It occurs when the retina is incompletely developed and blood vessels have not fully grown. The summary discusses screening criteria and stages of ROP diagnosis using the International Classification. Treatment options include cryotherapy, laser photocoagulation, anti-VEGF injections, and surgery. Clinical trials demonstrated that early treatment of high-risk prethreshold ROP reduces unfavorable visual outcomes.
This document provides a review of literature on diabetic macular edema (DME). It summarizes key studies on the pathophysiology and treatment of DME, including the Early Treatment Diabetic Retinopathy Study (ETDRS), trials of intravitreal corticosteroids, anti-VEGF drugs, and combination therapies. Major studies discussed include DRCR.net, PACORES, RESOLVE, BOLT, RIDE, and RESTORE trials which evaluated laser photocoagulation, corticosteroids, ranibizumab, bevacizumab, and combination therapies for treating DME. The document concludes anti-VEGF drugs like ranibizumab and bevacizumab
This document provides guidance on managing failing blebs after glaucoma surgery. It discusses risk factors for bleb failure, the histology of functioning vs failed blebs, typical appearances of failed blebs, identifying the cause of failure as internal or external blockage, and various management techniques. These include increasing digital pressure, medications, laser suture lysis, and bleb needling with or without anti-metabolites like mitomycin C or 5-fluorouracil to restore bleb function and control intraocular pressure. Complications of bleb needling are also reviewed.
This document discusses various vitreous substitutes and intraocular gases used to replace the vitreous humor after surgery. It describes the anatomy and composition of the natural vitreous and ideal properties for substitutes. Common substitutes discussed include gases like air, sulfur hexafluoride and perfluorocarbons; liquids like silicone oil, perfluorocarbon liquids and semi-fluorinated alkanes; and experimental polymers and implants. The document compares different options and provides details on how each works, associated complications, and appropriate uses.
This document summarizes neurotrophic keratitis, a degenerative disease of the cornea characterized by impaired healing due to loss of corneal sensation. It discusses the causes including infections, medications, trauma and systemic diseases. Three stages of the condition are described from early punctate keratitis and epithelial defects to stromal ulceration and potential perforation. The role of sensory innervation in maintaining the corneal epithelium is explained through animal studies. Diagnosis involves rose Bengal staining and fluorescein evaluation, while treatment aims to promote re-epithelialization in early stages to prevent progression to stromal melting and perforation.
This document discusses minimally invasive glaucoma surgery (MIGS) procedures. It defines MIGS as glaucoma surgery that is ab interno, uses a small incision, spares the conjunctiva, causes minimal trauma and tissue disruption, has a high safety profile, allows for rapid visual recovery, and can be combined with cataract surgery. It then describes various MIGS procedures including trabecular micro-bypass stents, gonioscopy assisted transluminal trabeculotomy, excimer laser trabeculotomy, the iStent, and suprachoroidal shunts. It provides details on the mechanisms, surgical techniques, indications, and complications of these different MIGS procedures.
This document discusses various biological agents used to treat uveitis, including tumor necrosis factor inhibitors like infliximab, adalimumab, etanercept, golimumab, and certolizumab. It provides dosing information and potential adverse effects for each drug. Anti-interleukin therapies like daclizumab, anakinra, tocilizumab, rituximab, gevokizumab, and secukinumab are also summarized. Key points are provided on initiating and monitoring patients on biological therapies to help maximize efficacy and safety. Biologics are described as potent treatments for uveitis when conventional therapies have failed or been poorly tolerated.
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.
Diabetic retinopathy is a leading cause of blindness that is classified as non-proliferative or proliferative and can involve macular edema. Duration of diabetes is a major risk factor, and anti-VEGF therapy is now preferred over laser for center-involving macular edema. For severe non-proliferative diabetic retinopathy or non-high risk proliferative disease, careful follow up is important and early panretinal photocoagulation may be considered, while high risk proliferative disease requires prompt panretinal photocoagulation or alternative anti-VEGF treatment.
The document discusses visual field testing in glaucoma. It defines the visual field and perimetry, and describes the major types of clinical perimetry tests including full threshold, SITA standard, and SITA fast on Humphrey and normal, dynamic, and TOP strategies on Octopus. It explains parameters such as test patterns, reliability, age-corrected plots, tests like GHT and Bebie curve, and global indices including MD, PSD, SF, and CPSD. The purpose of visual field testing in glaucoma is to detect and monitor disease by measuring light sensitivity across the retinal field.
1. The document discusses the relationship between visual acuity and retinal thickness in diabetic macular edema (DME) as measured by optical coherence tomography (OCT). While visual acuity only modestly correlates with foveal thickness, DME affects the entire macula.
2. A study found that changes in OCT-measured central retinal thickness did not strongly correlate with changes in visual acuity in DME patients. Inflammation plays an important early role in the development of DME before fluid accumulation occurs.
3. Which anti-VEGF drug is best for DME treatment - ranibizumab, bevacizumab, or aflibercept - remains unclear based on real-world evidence,
Multifocal IOLs provide both near and distance vision without glasses by utilizing concentric zones of different optical powers (refractive MFIOLs) or diffractive properties to split light between two focal points. While eliminating need for glasses, they can cause visual side effects like glare and reduced contrast sensitivity. Careful patient selection and counseling, accurate biometry and surgical technique are important for successful multifocal IOL implantation outcomes.
This document presents a case study of a 27-year-old female patient with iridocorneal endothelial syndrome (ICE) in her left eye. Her symptoms included diminished vision and pain in the left eye for 2 months. Ocular examination revealed findings consistent with ICE including iris defects, irregular anterior chamber depth, and specular microscopy showing polymegathism with a silver beaten appearance in the left eye. The patient was diagnosed with refractive error in the right eye and ICE in the left eye. She was prescribed eye drops and followed up regularly, with her IOP remaining controlled.
Coats' disease is a rare eye condition characterized by abnormal blood vessels in the retina. It most commonly affects young boys under 10 years old. The document discusses the history, signs and symptoms, classification, diagnosis, differential diagnosis, and management of Coats' disease. Treatment options depend on the stage of the disease and aim to obliterate abnormal retinal vessels using laser photocoagulation, cryotherapy, surgery, or newer adjunct treatments like intravitreal anti-VEGF agents. Indian studies found Coats' disease patients often present with more severe vision loss and extensive retinal involvement compared to other populations.
This document provides an overview of vitrectomy, including a brief history, the key steps in a simple vitrectomy procedure, and descriptions of the equipment used. It discusses trocars and cannulas, sclerotomies, illumination sources, viewing systems, vitreous cutters, and vitreous removal. Advantages of smaller gauge vitrectomy instruments are also summarized.
Retinoschisis is a splitting of the neurosensory retina into inner and outer layers, causing visual field defects. Senile retinoschisis occurs in 5% of people over 20 and presents as bilateral, peripheral retinal elevations that may progress circumferentially. Juvenile retinoschisis is an X-linked condition causing macular schisis and peripheral retinoschisis from birth, leading to progressive vision loss over decades. Both types are generally asymptomatic aside from visual field defects but may develop complications like retinal detachment, vitreous hemorrhage, or neovascularization. Diagnosis involves OCT, FA, and ERG and management focuses on complications or calcium channel blockers for macular schisis
This document provides information on retinal lasers, including their mechanism of action, properties that distinguish them from normal light, types of tissue interaction, parameters that can be adjusted, delivery methods, and applications in treating various retinal conditions. It describes techniques like photocoagulation, photodynamic therapy, and transpupillary thermotherapy; the lasers and parameters used; and indications for treating diseases such as diabetic retinopathy, retinal vein occlusions, and wet age-related macular degeneration.
This document provides information on hereditary macular dystrophies and macular function tests. It begins by describing the anatomical landmarks of the macula, including the fovea and foveola. It then discusses psychophysical macular function tests such as visual acuity testing, color vision testing, photostress testing, and Amsler grid testing. The document also covers electrophysiological tests like electroretinography (ERG) which objectively measures retinal electrical activity in response to light. ERG testing analyzes the a-wave from photoreceptors and b-wave from bipolar cells.
Intraocular safety OF ANTIVEGF INJECTIONS IN THE EYEAjayDudani1
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
Anti VEGF cause regression of neovascularization.
There is no effect on the basic pathology responsible for neovascularization (hypoxia).
It’s the disease that is to be cured to prevent hypoxia and its effects.
They are a valuable ammunition in our armamentarium but alone are not curative of the condition.
They give us time & VALUABLE breathing space during which we can plan our course of further action.
The document summarizes guidelines and recommendations for screening, diagnosing, and treating retinopathy of prematurity (ROP). ROP is a leading cause of childhood blindness that affects premature infants. It occurs when the retina is incompletely developed and blood vessels have not fully grown. The summary discusses screening criteria and stages of ROP diagnosis using the International Classification. Treatment options include cryotherapy, laser photocoagulation, anti-VEGF injections, and surgery. Clinical trials demonstrated that early treatment of high-risk prethreshold ROP reduces unfavorable visual outcomes.
This document provides a review of literature on diabetic macular edema (DME). It summarizes key studies on the pathophysiology and treatment of DME, including the Early Treatment Diabetic Retinopathy Study (ETDRS), trials of intravitreal corticosteroids, anti-VEGF drugs, and combination therapies. Major studies discussed include DRCR.net, PACORES, RESOLVE, BOLT, RIDE, and RESTORE trials which evaluated laser photocoagulation, corticosteroids, ranibizumab, bevacizumab, and combination therapies for treating DME. The document concludes anti-VEGF drugs like ranibizumab and bevacizumab
This document provides guidance on managing failing blebs after glaucoma surgery. It discusses risk factors for bleb failure, the histology of functioning vs failed blebs, typical appearances of failed blebs, identifying the cause of failure as internal or external blockage, and various management techniques. These include increasing digital pressure, medications, laser suture lysis, and bleb needling with or without anti-metabolites like mitomycin C or 5-fluorouracil to restore bleb function and control intraocular pressure. Complications of bleb needling are also reviewed.
This document discusses various vitreous substitutes and intraocular gases used to replace the vitreous humor after surgery. It describes the anatomy and composition of the natural vitreous and ideal properties for substitutes. Common substitutes discussed include gases like air, sulfur hexafluoride and perfluorocarbons; liquids like silicone oil, perfluorocarbon liquids and semi-fluorinated alkanes; and experimental polymers and implants. The document compares different options and provides details on how each works, associated complications, and appropriate uses.
This document summarizes neurotrophic keratitis, a degenerative disease of the cornea characterized by impaired healing due to loss of corneal sensation. It discusses the causes including infections, medications, trauma and systemic diseases. Three stages of the condition are described from early punctate keratitis and epithelial defects to stromal ulceration and potential perforation. The role of sensory innervation in maintaining the corneal epithelium is explained through animal studies. Diagnosis involves rose Bengal staining and fluorescein evaluation, while treatment aims to promote re-epithelialization in early stages to prevent progression to stromal melting and perforation.
This document discusses minimally invasive glaucoma surgery (MIGS) procedures. It defines MIGS as glaucoma surgery that is ab interno, uses a small incision, spares the conjunctiva, causes minimal trauma and tissue disruption, has a high safety profile, allows for rapid visual recovery, and can be combined with cataract surgery. It then describes various MIGS procedures including trabecular micro-bypass stents, gonioscopy assisted transluminal trabeculotomy, excimer laser trabeculotomy, the iStent, and suprachoroidal shunts. It provides details on the mechanisms, surgical techniques, indications, and complications of these different MIGS procedures.
This document discusses various biological agents used to treat uveitis, including tumor necrosis factor inhibitors like infliximab, adalimumab, etanercept, golimumab, and certolizumab. It provides dosing information and potential adverse effects for each drug. Anti-interleukin therapies like daclizumab, anakinra, tocilizumab, rituximab, gevokizumab, and secukinumab are also summarized. Key points are provided on initiating and monitoring patients on biological therapies to help maximize efficacy and safety. Biologics are described as potent treatments for uveitis when conventional therapies have failed or been poorly tolerated.
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.
Diabetic retinopathy is a leading cause of blindness that is classified as non-proliferative or proliferative and can involve macular edema. Duration of diabetes is a major risk factor, and anti-VEGF therapy is now preferred over laser for center-involving macular edema. For severe non-proliferative diabetic retinopathy or non-high risk proliferative disease, careful follow up is important and early panretinal photocoagulation may be considered, while high risk proliferative disease requires prompt panretinal photocoagulation or alternative anti-VEGF treatment.
The document discusses visual field testing in glaucoma. It defines the visual field and perimetry, and describes the major types of clinical perimetry tests including full threshold, SITA standard, and SITA fast on Humphrey and normal, dynamic, and TOP strategies on Octopus. It explains parameters such as test patterns, reliability, age-corrected plots, tests like GHT and Bebie curve, and global indices including MD, PSD, SF, and CPSD. The purpose of visual field testing in glaucoma is to detect and monitor disease by measuring light sensitivity across the retinal field.
1. The document discusses the relationship between visual acuity and retinal thickness in diabetic macular edema (DME) as measured by optical coherence tomography (OCT). While visual acuity only modestly correlates with foveal thickness, DME affects the entire macula.
2. A study found that changes in OCT-measured central retinal thickness did not strongly correlate with changes in visual acuity in DME patients. Inflammation plays an important early role in the development of DME before fluid accumulation occurs.
3. Which anti-VEGF drug is best for DME treatment - ranibizumab, bevacizumab, or aflibercept - remains unclear based on real-world evidence,
Multifocal IOLs provide both near and distance vision without glasses by utilizing concentric zones of different optical powers (refractive MFIOLs) or diffractive properties to split light between two focal points. While eliminating need for glasses, they can cause visual side effects like glare and reduced contrast sensitivity. Careful patient selection and counseling, accurate biometry and surgical technique are important for successful multifocal IOL implantation outcomes.
This document presents a case study of a 27-year-old female patient with iridocorneal endothelial syndrome (ICE) in her left eye. Her symptoms included diminished vision and pain in the left eye for 2 months. Ocular examination revealed findings consistent with ICE including iris defects, irregular anterior chamber depth, and specular microscopy showing polymegathism with a silver beaten appearance in the left eye. The patient was diagnosed with refractive error in the right eye and ICE in the left eye. She was prescribed eye drops and followed up regularly, with her IOP remaining controlled.
Coats' disease is a rare eye condition characterized by abnormal blood vessels in the retina. It most commonly affects young boys under 10 years old. The document discusses the history, signs and symptoms, classification, diagnosis, differential diagnosis, and management of Coats' disease. Treatment options depend on the stage of the disease and aim to obliterate abnormal retinal vessels using laser photocoagulation, cryotherapy, surgery, or newer adjunct treatments like intravitreal anti-VEGF agents. Indian studies found Coats' disease patients often present with more severe vision loss and extensive retinal involvement compared to other populations.
This document provides an overview of vitrectomy, including a brief history, the key steps in a simple vitrectomy procedure, and descriptions of the equipment used. It discusses trocars and cannulas, sclerotomies, illumination sources, viewing systems, vitreous cutters, and vitreous removal. Advantages of smaller gauge vitrectomy instruments are also summarized.
Retinoschisis is a splitting of the neurosensory retina into inner and outer layers, causing visual field defects. Senile retinoschisis occurs in 5% of people over 20 and presents as bilateral, peripheral retinal elevations that may progress circumferentially. Juvenile retinoschisis is an X-linked condition causing macular schisis and peripheral retinoschisis from birth, leading to progressive vision loss over decades. Both types are generally asymptomatic aside from visual field defects but may develop complications like retinal detachment, vitreous hemorrhage, or neovascularization. Diagnosis involves OCT, FA, and ERG and management focuses on complications or calcium channel blockers for macular schisis
This document provides information on retinal lasers, including their mechanism of action, properties that distinguish them from normal light, types of tissue interaction, parameters that can be adjusted, delivery methods, and applications in treating various retinal conditions. It describes techniques like photocoagulation, photodynamic therapy, and transpupillary thermotherapy; the lasers and parameters used; and indications for treating diseases such as diabetic retinopathy, retinal vein occlusions, and wet age-related macular degeneration.
This document provides information on hereditary macular dystrophies and macular function tests. It begins by describing the anatomical landmarks of the macula, including the fovea and foveola. It then discusses psychophysical macular function tests such as visual acuity testing, color vision testing, photostress testing, and Amsler grid testing. The document also covers electrophysiological tests like electroretinography (ERG) which objectively measures retinal electrical activity in response to light. ERG testing analyzes the a-wave from photoreceptors and b-wave from bipolar cells.
Intraocular safety OF ANTIVEGF INJECTIONS IN THE EYEAjayDudani1
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
Anti VEGF cause regression of neovascularization.
There is no effect on the basic pathology responsible for neovascularization (hypoxia).
It’s the disease that is to be cured to prevent hypoxia and its effects.
They are a valuable ammunition in our armamentarium but alone are not curative of the condition.
They give us time & VALUABLE breathing space during which we can plan our course of further action.
This document summarizes anti-VEGF drugs used to treat retinal diseases caused by abnormal blood vessel growth. It discusses the role of VEGF in these diseases and introduces several anti-VEGF drugs including pegaptanib, bevacizumab, ranibizumab, and aflibercept. It provides details on the mechanism of action, safety profiles, and costs of these drugs and compares the efficacy and safety of bevacizumab and ranibizumab based on studies like CATT. The document serves as an educational reference on anti-VEGF therapies for retinal specialists.
anti-vegf explain about vascular endothelial growth factorEhsan732370
VEGF is a protein that stimulates blood vessel growth and increases permeability. It plays a role in retinal diseases by causing abnormal new vessel growth and retinal swelling. Anti-VEGF drugs work by blocking VEGF, thereby reducing vessel growth and leakage. Bevacizumab is a monoclonal antibody that inhibits VEGF and is commonly used off-label via intravitreal injection to treat wet age-related macular degeneration and other retinal conditions associated with abnormal vessel growth and leakage. While effective, it carries risks of adverse events like bleeding and high blood pressure.
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
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
This document summarizes DEMO Pharmaceutical's investments in biotechnology, including the development and production of monoclonal antibodies. It discusses:
- DEMO's plans to build a new state-of-the-art facility for monoclonal antibody development and production, including a bioacademy, with an investment of 100 million euros over 10 years.
- The manufacturing process for monoclonal antibodies, from cell line development through fill and finish.
- Quality control testing to ensure safety, identity, purity and potency of biologic drugs.
- Biosimilar development which progresses through comparative in vitro and clinical studies to demonstrate similarity to a reference product.
- The impact of DEMO's investments, which will create jobs,
Sustained Release Drug Delivery StudiesZach Brazel
1) The document discusses developing a sustained release drug delivery system using stealth liposomes to treat ocular angiogenesis by encapsulating anti-VEGF antibodies and prolonging their release time in the eye.
2) Current anti-VEGF treatments require frequent, expensive injections which increase risks like endophthalmitis. The authors have created stable stealth liposomes that can encapsulate proteins and release them slowly over 200-240 days to decrease treatment frequency and costs.
3) Their best liposome formulations had a particle size of 100-150nm, encapsulation efficiency of 85-92%, and sustained protein release over 6-8 months based on in vitro studies. This drug delivery system has potential to overcome issues with current treatments
Imugene is developing B-cell peptide vaccines called mimotopes that induce a patient's own B-cells to produce antibodies targeting specific cancer antigens. Their lead candidate, HER-Vaxx, is a mimotope therapy for HER2-positive cancers that is designed to mimic the Herceptin antibody. A completed Phase 1 trial in breast cancer demonstrated HER-Vaxx was safe and induced anti-HER-2 antibodies and immune responses. Imugene is now conducting a Phase 1b/2 trial of HER-Vaxx in combination with chemotherapy in HER2-positive gastric cancer patients with results expected in 2018. The document provides an overview of Imugene's novel mimotope platform and its
Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings o...sstrumello
Inger Mollerup, Vice President of Novo Nordisk A/S, testified before the Government Oversight and Reform Committee about establishing a pathway for approval of follow-on biologics. She argued that any pathway must require clinical trials to demonstrate safety because even minor differences in biologics can have major health consequences, as shown through Novo Nordisk's experience. She also stated that traceability and unique names are important for pharmacovigilance, and that interchangeability is not supported by current science given potential immunogenicity differences between products.
The document summarizes key points about pharmacovigilance from an industry perspective. It discusses the historical milestones that demonstrated the importance of pharmacovigilance. It then describes pharmacovigilance processes, including adverse event reporting, signal detection, and risk management plans. Finally, it outlines the new EU legislation's aim to strengthen and rationalize the EU pharmacovigilance system through requirements for pharmacovigilance systems and increased transparency.
Anti-VEGF agents such as bevacizumab, ranibizumab, pegaptanib, and aflibercept are used to treat retinal diseases caused by abnormal blood vessel growth due to VEGF overexpression. They work by inhibiting VEGF to prevent new blood vessel proliferation and leakage. Common uses include treating wet age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and retinopathy of prematurity. Ranibizumab and aflibercept are approved by the FDA, while bevacizumab is commonly used off-label. Monthly intravitreal injections are typically required initially, then treatments are extended based on disease response. Adverse events include inflammation, increased intraocular pressure, and
This document discusses new treatments for age-related macular degeneration (AMD), which is a leading cause of blindness. It outlines several anti-inflammatory therapies, anti-oxidative stress therapies, visual cycle modifying agents, and choroidal blood flow enhancing agents that are being studied in clinical trials to treat dry AMD. It also discusses emerging therapeutic options for wet AMD such as anti-platelet-derived growth factor agents, new anti-VEGF drugs, and sustained drug delivery devices. Finally, it reviews several new intraocular lens designs that aim to improve vision for patients with AMD through magnification or image displacement.
This 3-day event is the meeting place for international and domestic scientists to share case studies and project updates, showcase new techniques and form collaborations that pave the way towards the future of China’s biopharmaceutical industry.
VEGF inhibitors are used to treat eye diseases characterized by abnormal blood vessel growth such as age-related macular degeneration and diabetic retinopathy. Bevacizumab, ranibizumab, aflibercept, and pegaptanib are VEGF inhibitor drugs administered via intravitreal injection that bind to VEGF and inhibit its activity. They have been shown to reduce vascular permeability and slow disease progression. Common side effects include hypertension, bleeding, and eye inflammation. VEGF inhibitors are an important treatment option for neovascular eye diseases.
Drug development and discovery in biologicsAshish sharma
This document provides an overview of drug development and discovery in biologics. It discusses key topics such as biologics and biosimilars, the integrated discovery and development process of antibodies, the market status and typical manufacturing process of biologics, their therapeutic roles and biological targets in therapy. Some of the challenges in biologics development include the complex manufacturing process, safety implications, immunogenicity, and limited shelf life. Regulations of biologics in India are outlined. Recent FDA-approved biologics are also mentioned. In conclusion, biologics and small molecules are seen as complementary approaches for drug development.
1) Avalanche Biotechnologies is developing gene therapy treatments for eye diseases using its Ocular BioFactoryTM platform. Its lead product AVA-101 has shown promising clinical results for wet age-related macular degeneration (AMD) with patients gaining or maintaining vision with few additional treatments needed over one year.
2) Avalanche has an integrated gene therapy discovery, development and manufacturing platform and a pipeline of other programs including a collaboration with Regeneron. It has an experienced management team in the areas of gene therapy and ophthalmology.
3) The company highlights its potential to develop one-time transformative treatments for major sight-threatening diseases in ophthalmology using its Ocular BioFactoryTM platform
Drug Types: Biosimilars, generics and more. December 2017 Webinar 12122017Fight Colorectal Cancer
This document provides information about an upcoming webinar on drug types including biosimilars and generics. It outlines details like the speaker, how to ask questions during the webinar, and instructions for accessing the webinar archive and following along on Twitter. It also provides brief bios of the speaker and gives technical instructions for participating in the webinar platform. Finally, it lists some resources and includes a standard disclaimer.
The conference will provide an interactive networking forum to both further develop and answer your queries through a vibrant exhibition room full of technology providers showcasing their technologies and other solutions, poster presentation sessions, expert led case study presentations, a high-level panel discussion, a round table discussion session, and interactive Q&A sessions from a 40-strong speaker faculty examining topics on 4 separate tracks outlined below.
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.
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.
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
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
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
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
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
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.
Hiranandani Hospital in Powai, Mumbai, is a premier healthcare institution that has been serving the community with exceptional medical care since its establishment. As a part of the renowned Hiranandani Group, the hospital is committed to delivering world-class healthcare services across a wide range of specialties, including kidney transplantation. With its state-of-the-art facilities, advanced medical technology, and a team of highly skilled healthcare professionals, Hiranandani Hospital has earned a reputation as a trusted name in the healthcare industry. The hospital's patient-centric approach, coupled with its focus on innovation and excellence, ensures that patients receive the highest standard of care in a compassionate and supportive environment.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- 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
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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
1. Treatment Options in
Medical Retina: Where do
we stand?
DR. AJAY DUDANI
PROF- K J SOMAIYA MEDICAL COLLEGE
MUMBAI RETINA CENTRE
ZEN EYE CENTRE
2. Retinal conditions – Current
scenario
Source: https://theophthalmologist.com/issues/0317/its-in-their-bones/
3. VEGF-A: key mediator of angiogenesis
and vascular permeability.......
The development of antivascular endothelial growth factor (anti-VEGF) has
revolutionised the treatment of a plethora of ocular angiogenic disease processes.
Tah et al. Anti- VEGF Therapy and the Retina – An Update; Journal of Ophthalmology 2015
4. Evolution of Anti-VEGFs
Hypothesized - a diffusible, hypoxia-
induced, angiogenic “factor X” was
responsible for iris and retinal
neovascularization associated with
ischaemic retinopathies.
initiated phase 1 trials for the
development of an anti-VEGF molecule
(bevacizumab)
Discovered a candidate
glycoprotein and termed
vascular permeability factor
Discovered a tumour-derived factor
named vascular permeability factor
(VPF), which was responsible for
inducing vascular permeability
Decades later
1948 Michaelson
1989 Leung et al.
1990 Keck et al.
The diffusible,
hypoxia induced,
endothelial cell-
specific factor
VEGF
conceivably
represents
Michelson’s
retinal tissue
“factor X”
Elevated levels of
VEGF in ocular
fluids from
patients with active
neovascular ocular
disease were found
compared with
ocular fluids with no
vascularisation.
Simultaneous Research showed
All the
evidence of
angiogenesis
points to the role
of VEGF in ocular
neovascularisatio
n
1997 Genentech
Tah et al. Anti- VEGF Therapy and the Retina – An Update; Journal of Ophthalmology 2015
5. Evolution of Anti-VEGFs....contd
2003 - 2004
Furthermore, with the knowledge that
VEGF played a significant role in
neovascular AMD, FDA approved
pegaptanib (Macugen) was created,
making it the first antiangiogenic
therapy for ocular neovascularisation
Bevacizumab approved for the
treatment of colon cancer in
combination with chemotherapy
– based on successful results
from phases 2 and 3 trials.
2004 - 2005
Believing that bevacizumab would not
efficiently diffuse through the retina to
reach the choroid, Genetech decided
to generate a truncated alternative
molecule (Ranibizumab)
2007
Ranibizumab (Lucentis) was approved based on data
from two large Phase III clinical trials:
• MARINA (minimally classic/occult trial of the anti-
VEGF antibody ranibizumab in the treatment of
neovascular AMD)
• ANCHOR (anti-VEGF antibody for the treatment of
predominantly classic choroidal neovascularisation
in AMD) trials
• 1st Anti-VEGF for intraocular use
2011
Regeneron developed a chimeric fusion
protein (Aflibercept) that acted as a
decoy receptor to sequester VEGF and
thereby block its biological effects
Tah et al. Anti- VEGF Therapy and the Retina – An Update; Journal of Ophthalmology 2015
Since its approval in 2006, ranibizumab has revolutionized the treatment of retinal diseases
7. Rbz Innovator : supported by a large amount of
clinical evidence with 17 million injections
across indications
• Rbz Innovator is the only anti-VEGF agent which has:
1. Novartis Pharma AG. Accentrix Summary of Product Characteristics, September 2014; 2. Rofagha S, et al. Ophthalmology 2013;120:2292-9; 3. Novartis Pharma AG. Press
release September 2013. http://www.novartis.com/newsroom/media-releases/en/2013/1731649.shtml; 4. Bloch SB, et al. Am J Ophthalmol 2012;153:209-13; 5. Brand C, et
al. Presented at ARVO, 5 May 2013, Seattle, WA, abstract #3831
Most extensive patient
follow-up program
Patient-years,
from continued
post-marketing,
real-world data, and
pharmacovigilance
studies4,5
Years of
long-term data
available2
ANCHOR
SEVEN-UP
PIER
SAILOR
SUSTAIN MONT BLANC
MARINA
FOCUS
EXTEND EXCITE
GEFAL
HARBOR
WAVE
LUMIÈRE
CATT
IVAN VIEW
BRAMD
COMPASS
LUMINOUS
SAVE
SECURE
LAST
FUSION
HORIZON
PrONTO
Largest number
of clinical trials
Patients included
in the extensive
clinical trials
program3
Largest amount
of patient data
Rbz Innovator has a well-defined efficacy and safety profile supported by
clinical trials and real-world data
Number of indications
approved for treatment1
Largest number of
approved indications
nAMD
Myopic CNV
DME
CRVO
BRVO
8. Real-world evidence shows over 70,000
patients have been treated with
ranibizumab innovator
Cumulative
number
of
patients
*Except other choroidal neovascularization. †Includes n=401 eyes
1. Cohen SY, et al. Graefes Arch Clin Exp Ophthalmol 2011;249:521–7; 2. Shona O, et al. Clin Exp Ophthalmol 2011;39:5–8; 3. Pushpoth S, et al. Br J Ophthalmol 2012;96:1469–73; 4. Novartis, Data
on file
Cumulative number of patients included in
ranibizumab real-world studies (all indications)*1-4
9. Anti-VEGFs – Current Status
Innovator biologics like
1. Ranibizumab
2. Aflibercept
3. Bevacizumab (Off-label) are well known and successful.......
In the world of ophthalmology,
Biosimilars
1. Ranibizumab
2. Bevacizumab
Now.......companies are developing anti-VEGF biosimiliars in attempts to get a
foothold in the anti-VEGF market....
Are biosimilars the same as Innovator biologics?
10. Biologics Are Large, Protein-Based
Therapeutics That Vary in Size and
Complexity
Small Molecule Biologics
Acetylsalicylic
acid1
~ 180 daltons Insulin2
~ 5,700 daltons
Growth hormone3
191 amino acids
~ 22,000 daltons
Monoclonal antibody4
~ 1,300 amino acids
~ 150,000 daltons
Increasing Complexity
1. Aspirin (acetylsalicylic acid) prescribing information, Bayer.
2. Insulin product information, Sigma-Aldrich. www.sigmaaldrich.com/content/dam/sigma-
aldrich/docs/Sigma/Product_Information_Sheet/2/i6634pis.pdf. Accessed February 6, 2017.
3. Online Mendelian Inheritance in Man.
www.omim.org/entry/139250?search=human%20growth%20hormone&highlight=hormone%20growth%20human. Accessed Feburary 6,
2017.
4. Chennamsetty N, et al. mAbs. 2009;1:580-582
11. What Is a Biosimilar?
• Undergone rigorous analytical and clinical assessment, in
comparison to its reference product
• AND
• Been approved by a regulatory agency according to a specific
pathway for biosimilar evaluation
A biosimilar is a “copy” of a commercially
available biopharmaceutical (reference product)
that no longer is protected by patent which has:
A biosimilar is “highly similar” to its reference
product in physicochemical characteristics,
efficacy, and safety.
Dörner T, et al. Ann Rheum Dis. 2016;75(6):974-982.
12. Biosimilars Are Not…
Woodcock J, et al. Nat Rev Drug Discov. 2007;6(6):437-442.
→ Structurally different from originally
licensed biopharmaceutical
→ Intended to improve performance
while preserving mechanism of action
→ Examples
Infliximab and adalimumab
Filgrastim and pegfilgrastim
→ Not considered to be biosimilar
Second-Generation
(or Biobetter)
Generic Drugs
→ Small-molecule drugs, that are
less complex than biosimilars
→ Manufacturing process is several
orders of magnitude less complex
→ Regulated under different
legislation
14. Biologics: Drug Substance
Production Process
START
Vectors to
insert the gene
Gene sequence
coding for
protein
Host cells to
grow the protein
END
Biophysical characteristics
of final drug substance
Lengthy and complex
purification process
Fermentation
with very precise
culture conditions
Factors influencing properties of the molecule:
• Time, pH, temperature, culture media, oxygen
levels/lactic acid accumulation
Properties most frequently affected:
• Carbohydrates, ratios of charged species,
aggregates
Factors influencing properties of the
molecule/product:
• Removal of host cell DNA and proteins
• Removal of fragments and aggregates
• Concentration of the protein
• Final formulation buffer
Liu HF et al. mAbs. 2010;2;(5):480-499
Li F. et al. mAbs 2010;2(5):466-477
15. Manufacturing Biologics – why is it
so difficult ?
• A biological typically requires around 250 in process
tests during manufacturing as compared to around 50
for routine generics
• To ensure high quality and consistency in final product ,
high level of monitoring and testing required during
production.
16. Biologics Manufacturing Control at
EveryStep
In ProcessTestingData From EveryProcess Step
CellBank Bioreactor Harvest Chromatography
1, 2, 3
Virus Filter Concentration
Bottling
FinalTests
Purification
Cell Culture Final Dosage Form
Forcomparability, the innovator hasarich testing database from every in process
step of every batch, the biosimilar only hasaccessto the finalproduct
17. Biosimilars and Twins:
Identical DNA, Minor differences in Features
• Theactive ingredient of abiosimilar can at best only resemblethat of
the innovator product
• How an innovator makesits biologic can never be duplicated down to the
last detail; abiosimilar is made using cells, materials and processesthat
differ from the innovator product
• Thisis true even if abiologic and its biosimilar start from the samegenetic
blueprint, in much the sameway asidentical twins, despite the same
genes, have different fingerprints
18. Different vectors to
insert the gene
Different host cells to grow
the protein
Different fermentation/culture
conditions
Different downstream processing
Different biophysical characteristics in final
product
19. Accumulated Experience and Knowledge
Generates Sustainable Quality and Predictability
YEAR 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Innovator
Development
Discovery and
Target Validation
Cell Line,
Process
Development
Process Characterization,
Validation
Process monitoring, Scale and Site changes, Comparability Protocols,
Process consistency Assurance
Characterization of Molecule, Structure
/Function Studies, Justify and Establish
Specifications
Deep understanding of Product Properties, Comparability Protocols to assure consistent product
Non-clinical Studies
Ph 1
clinic
als
Phase 2
Clinicals Phase 3Clinicals
BLA/
MAA Clinical Studies for additional Indications
Pre-Approval SafetyDatabase
Post-Approval Safety Database, Post-Approval Phamacovigilence, Post-
Marketing Observational Stuides, Post-Marketing Safety Studies
YEAR 1 2 3 4 5
Biosimilar
Development
Cell Line, Process
Development,
Characterization
Analytical
Characterization,
Establsih Specifications
Non-
Clinical
Studies
Clinical studies
BLA/
MAA
Pre-Approval SafetyDatabase
21. Manufacturing Biosimilars
Even small changes in production – minor equipment and
environmental variations can :
• Cause significant changes in behavior of cells
• Change in the fragile 3-dimensional structure of the
protein
• Change in quantity of acid-base variants and
glycosylation
• Impact the safety and effectiveness of the Biologic
23. Interchangeability
“Biosimilar to the U.S.-licensed
reference biological product …
expected to produce the same
clinical result as the reference
product in any given patient.”
“For a biological product that is administered
more than once to an individual, the risk in
terms of safety or diminished efficacy of
alternating or switching between use of the
biological product and the reference product
will not be greater than the risk of using the
reference product without such alternation or
switch”
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalAppli
cations/TherapeuticBiologicApplications/Biosimilars/ucm411418.htm. Accessed 19th Feb 2016
Note : The interchangeable product may be substituted for the reference product without the intervention of the health care
provider who prescribed the reference product.
(biosimilar drug should
neither increase AEs nor
decrease efficacy when
switched from the
reference drug)
25. Steps involved in Approval of Similar
Biologic
Physicochemical
data
Pre-clinical
Studies
Clinical (PK/PD)
studies
Confirmatory
clinical safety
and efficacy
studies
Safety and
Immunogenicity
Data
• One or more adequately
powered, randomized,
parallel group, blinded
confirmatory clinical
safety and efficacy trials
are desirable based on
the comparability
established during
preclinical and PK / PD
studies
• Pharmacodynamic
Studies
• Toxicological
Studies
• Both pre-approval and post-
approval assessment of
safety is desired to be
conducted for similar
biologic.
• Regarding pre-approval
safety assessment,
comparative pre-approval
safety data including the
immunogenicity data is
required for all similar
biologics
26. • Strong need for regulations governing biosimilars
• Implementation of an abbreviated licensure pathway for biological
products presents challenges, given the associated scientific &
technical complexities
• European Union has regulations in place for quite some time for
approving biosimilars
• US & India have recently covered these under their respective Acts
by bringing in applicable guidelines for their evaluation & overall
regulation
Status of Regulations for Biosimilars
Globally
28. Strength of Evidence
Meta-
analysis
Randomized
Clinical
Trials
Cohort studies
Case control studies
Case reports
Editorials/Expert Opinions
Animal research/ In-vitro studies
1
2
3
4
5
Levels of evidence
http://www.dentalcare.co.uk/dental-professional-education/dental-courses/ce-
311/evidence-based-decission-
making.aspx?ModuleName=coursecontent&PartID=4&SectionID=-1. Accessed on 30th Sept
2016
Currently all the
data of
Ranibizumab
biosimilar fall into
this level
Ranibizumab
Innovator
29. Occult CNVM 15 YR STUDY –
BILATERAL RAP -45 INJECTIONS
• 82 year old male
• Strong family history of AMD
• LE – Diagnosed with AMD 14 years ago(2001), Underwent 2 TTT’s, 3
PDT’s with IVTA, now has macular scar with Vn of HM
RE – Has had 1 PDT (Nov 2005) for extra foveal RAP lesion and 36
injections of Lucentis in the past 11 year
• OCT MONTHLY
• EXTENT AND TREAT-ONLY INJECT WHEN FLUID
• LUCENTIS TACHYPHYLAXIS?
• RE AFTER SWITCH TO EYLEA -6 EYLEA INJ OVER 5 YRS
• Repeat eylea after 4 months ON PRN BASIS
• LAST EYLEA 2WEEKS AGO AFTER 12 MONTHS
• VISION 6/9 N6
• GEOGRAPHIC ATROPHY
30. COMPARE PRE AND POST VEGF -RAP
• PRE VEGF EYE—PL
• POST VEGF 6/9 N12
• DOES THE LEAK EVER STOP
• STARTS AS FLOOD
• THEN A DRIZZLE
• ENDS AS A MINOR TRICKLE
• VEGF IS THE DRIVER
• ANTIVEGF IS THE GLUE
• WATERPROOFING THE RETINA
• DR FIXIT
33. Serial OCTs - PEDs with fluid
Sep 05 – PDT
done
May 06 – post lucentis
– 3 injections at 2
monthly intervals
May 06 – fluid 6
months later –
Lucentis started
34. Serial OCTs
May 07 – Fluid 8 months
after last injection –
needed injection every 3
months since..
Jan 09 – eg of OCT post
injection
March 09 – fluid in
3 months –
Thickening of
same parafoveal
area every 3
months
35. Serial OCT’s – Last injection
July13
July 2013 – pre- injection
Feb’13 - extra foveal site
40. ANTI VEGF SIDE -EFFECTS
• DID IT LEAD TO CHORIODAL ATROPHY
• GEOGRAPHIC ATROPHY
• GLAUCOMA
• HEART ATTACK
• HYPERTENSION
• CENTRAL SCOTOMAS
• SLOW READING SPEED
• LOSS OF CONTRAST SENSITIVITY
• EXTENT AND TREAT
41. Summary
• Anti-VEGF medications have revolutionized the treatment of
exudative AMD over the past 2 decades and patients with a
potentially blinding disease have been able to regain vision.
• While there is still no clear-cut best treatment regimen,
evidence suggests individualized treatments may be safer
and more efficient.
• The "treat and extend" protocol seems to offer the most
favorable alternative to the monthly regimen with a goal
being to extend the interval between visits to maintain an
exudation-free macula with the fewest number of visits and
injections
• There still remain several unanswered questions regarding
nAMD treatment such as the interval by which "treat and
extend" protocols should be extended at each visit, how
42. Ranibizumab vs biosimilar
Parameter Bio-similar Study Ideal Standard
Duration of
the Study
Just 3 months Minimum of 1 year follow up is necessary and ideally
landmark studies like CATT & IVAN have taken the 2 year
follow up to compare the safety between bevacizumab
and ranibizumab.
Endpoint % of patients with loss of <15 letters Current studies evaluate BCVA gain
Number of
Patients in
the study
The study with Bio-similar has only
100 patients.
Biosimilar arm 75 and ranibizumab
arm 25.
A minimum of 30 patients is required in any arm of a trial
for statistical significance and the ranibizumab arm is
under –represented.
Sample sizes for most H2H studies of Anti-VEGF have
been around 200- 300 patients
Ranibizumab and its biosimilar have been studied in one
single trial and that too in patients of AMD only.
http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=7625&EncHid=&userName=ranibizumab.
Accessed on 19/02/2016
43. RE-ENACT Study (Retrospective,
Multicentre, Observational study on Wet AMD)
45
Did not capture the complete information on adverse
events in the medical records and hence, not analyzed in
this subgroup
46. Recent Report of Eye Inflammation with Rbz
Biosimilar, Company Recalls Batch for QC Testing
48
Patel D. Patients report eye inflammation, Intas recalls its drug batch. The Indian Express. April
3, 2017. http:// indianexpress.com/article/business/companies/undertaking-detailed-analysis-
patients-report-eye-inflammation-intasrecalls-its-drug-batch-4596914/. Accessed April 11, 2017
With some patients reporting
Inflammation in their eyes due to Rbz
Biosimilar, the company has advised the
docs to not to use any drug of this of this
particular batch. It has also recalled this
batch from the market to undergo internal
testing at its QC lab
47. VRSI Issued Alert on Ranibizumab
Biosimilar Second Time In a Row
49
Dear Members, there had been reports of Intraocular
Inflammation from various parts of India after IV Rbz Biosimilar
of a company. Company has advised not to use Rbz Biosimilar
Inj. of batch no 18020020. VRSI is gathering more facts on this
situation.
It is advised that all members to be alert and exercise
abundance of precaution with other batches of the biosimilar
also. Please report any adverse Incidents to VRSI at
secretaryvrsi@gmail.com
48. FDA Inspection of Biosimilar Plant
50
Observation-1: Lab reports are deficient in that they do not
include complete record of all data obtained during testing
Observation-2: Appropriate controls are not exercised over
computers or related systems. There was failure to
maintain backup file of data entered into computer or
related system
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/cder
foiaelectronicreadingroom/ucm567595.pdf
49. 51
• Observation-10: Building used in mfgd., processing, packing or
holding of drug products are not free of infestation by birds
• Observation-11: Cell bank were not maintained under appropriate
storage monitoring conditions designed to maintain viability and
prevent contamination and records of the vials from the cell bank and
storage conditions were not maintained
FDA Inspection of Biosimilar Plant
https://www.fda.gov/downloads/drugs/guidancecomplianceregulato
ryinformation/cderfoiaelectronicreadingroom/ucm567595.pdf
50. USFDA – approved innovator
Manufacturing Site
52
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process
51. Summary
• With patent expiration of innovator products, biosimilars will
increasingly become available
• Awareness of the deviations between biosimilars &
innovator products in terms of efficacy, safety &
immunogenicity is essential for proper prescription & safety
of the patients
• How similar is similar enough?