Retinal laser in opthalmology

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A presentation on Retinal laser in opthalmology from Dr. Agarwal's Eye Hospital , in Kalpavriksha - 2012 , Chennai

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  • 1. Intra-vitreals in Ophthalmology Dr. Atul Dhawan (M.S., F.E.R.C.) Vitreo-Retina Consultant Dr. Agarwals Retina Foundation Chennai

2. In 1895, Deutschmann injected transplanted rabbit vitreous, and Ohm injected air in the vitreous cavity for the repair of RD. Subsequent decades, the use of IVI was limited to administration of saline and air. In the 1960s and 1970s, long-lasting gases were developed for the repair of complex RD. 3. The modern era of IVI began in the early 1970s with the investigation of the blood ocular barriers . The results of these investigations stimulated the use of IVI of antibiotics for treatment of endophthalmitis and steroids for treatment of intraocular inflammation to bypass anatomical barriers in the eye. 4. This concept heralded the advent: Anti-inflammatory and antineoplastic drugs in the 1970s to 1980s Antivirals :1980s to 1990s Triamcinolone acetonide (TA) and Vascular endothelial growth factor (VEGF) inhibitors in the 2000s. 5. COMMONLY USED IVI INJECTION Anti-infective (antibiotic, antifungal, and antiviral) Anti-inflammatory :nonsteroidal antiinflammatory,steroids,immunomodulators Gas Anti-VEGF 6. Anaesthesia Topical anesthesia (66.6%) Subconjunctival (33.3%) 7. Procedure The injection site : infero-temporal quadrant in the pars plana is 3-4 mm posterior to the limbus. The needle aimed at the midvitreous The needle is removed with the application of a cotton-tipped applicator over the sclerotomy site to minimize reflux of material. Postinjection course of topical antibiotics typically lasts for 3-7 days. 8. Post injection check up 9. Delivery of Anti-infective Agents 10. Endophthalmitis: for a surgeon 11. Endophthalmitis severe Intraocular inflammation predominantly involving the inner coat e.g. Retina and vitreous Intraocular colonization by microorganisms Worst complication of ophthalmic surgery 12. With this event the hopes of the patient vanish, confidence of the operating surgeon is shattered, and there is always a lurking fear of possible medico-legal implications. 13. Antibacterial drugs 14. Aminoglycosides. The aminoglycoside antibiotic streptomycin, gentamicin, kanamycin, tobramycin, amikacin, and netilmicin. Chemical composition of an organic base with amino sugars Synthesized : fungal organisms. Antibiotic activity against both gram-positive and gram negative bacteria due to interfere with synthesis of ribosomal proteins. 15. Amikacin 16. Amikacin is the aminoglycoside of choice for human endophthalmitis DOSE : 400 microgram/0.1 ml 17. Mechanism of action: Bactericidal Bind to 30S/50S/30S-50S interface Leads to misinterpretation of code Adding of defective protein in cell wall Cell wall integrity lost 18. Vancomycin 19. Glycopeptides Vancomycin. Intravitreal vancomycin is the drug of choice for endophthalmitis caused by gram-positive organism . Dose : 1 mg/0.1 mL Inhibit bacterial cell wall synthesis 20. Mechanism of action: Bactericidal 21. Always Remember. Caution in patients with silicone oil, because nontoxic concentrations of this drug may become toxic after IVI in postvitrectomy, silicone-filled rabbit eyes. The threshold for ocular toxicity in rabbits decreased to one quarter of the nontoxic dosage in an unoperated eye compared with silicone-filled eyes. 22. Cephalosporin Ceftazidime and Cefotaxime has more activity against gram- negative organisms but are less active against gram-positive bacteria, especially Staphylococcus. Cefazolin is currently not recommended for treatment of endophthalmitis due to increase in resistant organisms. Inhibit cell wall synthesis : bactericidal 23. AMPHOTERICIN B. 24. Amphotericin B fungistatic and fungicidal antibiotic synthesized from Streptomyces nodosus strains most effective antifungal drug available. (0.005 mg in 0.05 mL) is the drug of choice. 25. Mechanism of action binds to ergosterol in cell wall of fungi localized lysis pores in cell wall leakage of K+ ions osmotic imbalance cellular death 26. Voriconazole newer azole antifungals that contain a third nitrogen on the azole ring second-generation synthetic derivative of fluconazole. The minimal inhibitory concentration for Candida species, Aspergillus fumigatus, Histoplasma capsulatum,and Fusarium organisms is much lower than others. 27. Antiviral Agents Intravitreal antiviral medications have been used for treatment of viral retinitis. Typically occurs in immunosuppressed patients suffering from debilitating illnesses Cancer or AIDS or in patients receiving systemic corticosteroids Immunosuppressive medications for organ transplantattion. 28. Acyclovir 29. Nucleoside Analogs Acyclovir Acyclovir is a nucleoside analog. Significant activity against herpes simplex viruses Because it is activated in vivo by the virus specific enzymes in infected cells. Acyclovir is not toxic to noninfected cells. Acyclovir is one of the first antiviral agents to be studied for IVI. to 240 microgram were safe to all ocular structures. 30. Mechanism of action 31. Ganciclovir 32. The first antiviral agent to be used with IVI against CMV retinitis in AIDS patients. A nucleoside analog of acyclovir with a 10- to 100-fold greater activity against CMV than Acyclovir. Mechanism of action: same as Acyclovir 33. Dose : induction -2 mg/0.1ml 0.1 ml injected 2 times per week for 3 wks Maintanance - 2mg/0.1 ml once a week 34. VITRASERT 35. VITRASERT Gancicovir implant. Provides local sustained conc. Of the drug with decrease risk of systemic SE without repeated injections. Therapeutic levels upto 8 months 4.5 mg drug in 2.5 mm pellet completely coated by drug permeable poly vinyl alcohol and incompletely coated with impermeable ethyl vinyl acetate. Releases drug at rate of 1 micro gm/hr. Mean intravitreal conc. achieved is 4.1 microgm/ml. 36. Corticosteroids 37. Specially useful against the inflammatory reaction associated with endophthalmitis Corticosteroids reduce macular edema in: Diabetic macular edema (DME) Pseudophakic CME Macular edema associated with vein occlusions 38. Dexamethasone Intravitreal dexamethasone safe to all ocular structures. Dexamethasone has a relatively short vitreous half-life thus, it is less likely to cause increased IOP than other steroids 0.4 mg 0.1 ml. 39. Ozurdex Drug Delivery Technology O O O O CH3 CH3O O O O Sites of hydrolytic cleavage during biodegradation HO OH HO OH CH3 O O Polymer DegradationDrug Release O O O O CH3 CH3O O O O Sites of hydrolytic cleavage during biodegradation HO OH HO OH CH3 O O Lactic Acid Glycolic Acid H2O, CO2, and natural metabolites Polymer DegradationDrug Release Lactic Acid Glycolic Acid Water and Carbon Dioxide Biodegradable Implant Gradually Transforms Into Water and Carbon Dioxide 40. A biodegradable dexamethasone implant Drug incorporated into polymer matrix Sustained medication release Polymer matrix gradually breaks down into inert compounds 41. Ozurdex Applicator and NOVADUR implant 42. Rod shaped tiny implant 0.45 mm in diameter and 6 mm in length Contains 0.7mg of Dexamethasone (preservative free) 43. Changes in Polymer Matrix Over Time After 3 Weeks Before Implantation 44. TRIAMCENOLONE ACETATE Intermediate acting steroid Dose 4 mg intraviteal injection Use: recalcitrant macular edema in choroidalneovascularization to visualize vitreous in clear gel vitrectomy 45. FLUCINOLONE ACETATE 46. RETISERT is indicated for the treatment of chronic non-infectious uveitis affecting the posterior seg. 47. RETISERT 48. Implant : one tablet of 0.59 mg of fluocinolone acetonide. RETISERT is designed to release fluocinolone acetonide at initial rate of 0.6 g/day, decreasing over the first month to a steady state between 0.3-0.4 g/day over approximately 30 months. 49. Delivery of Anti-VEGF Agents 50. SITES WHERE WE CAN HIT 51. MILESTONES IN VEGF 19481958 Michaelson, Ashton, and Wise contribute to factor X hypothesis 1989 Ferrara clones VPF and identifies it as an angiogenesis factor; VPF is rechristened VEGF 1997 First clinical trials of antiangiogenic therapy in cancer patients initiated 1999 First anti-VEGF therapy tested in humans with AMD 52. Properties of VEGF 1. Stimulator of angiogenesis 2. Potent inducer of vascular permeability 3. Proinflammatory effects 4. Neuroprotective effects 53. Pathologic VEGF activates CNV cascade Ambati et al, Surv Ophthalmol, 2003; Ferrara et al, Nat Med, 2003; Ishida et al, J Exp Med, 2003; Witmer et al, Prog Retin Eye Res, 2003; Zarbin, Arch Ophthalmol, 2004. Neovascular AMD Pathologic VEGF Breakdown of Blood-Retinal Barrier Monocyte Recruitment Cytokine and Protease Release Initiating Stimuli Angiogenesis Pathologic Neovascularization 63 54. VEGF in pathologic ocular neovascularization Neovascular AMD Diabetic retinopathy Retinal vein occlusion Retinopathy of prematurity Corneal neovascularization Iris neovascularization 55. WHAT IS Bevacizumab? 56. AVASTIN MOLECULE 57. AVASTIN (BEVACIZUMAB) CLEAR TO SLIGHTLY OPALESCENT STERILE SOLUTION PH 6.2 Avastin half life in vitreous =4.32 days 58. SIDE EFFECTS OF AVASTIN.. 59. OCULAR SIDE EFFECTS RPE TEAR LENS INJURY CORRNEAL ABRASION CHEMOSIS OCULAR INFLAMMATION INCREASED INTRA OCULAR PRESSURE 60. SYSTEMIC SIDE EFFECTS CEREBRAL INFARCTION INCREASED SYSTOLIC BLOOD PRESSURE FACIAL SKIN REDNESS 61. Ranibizumab 62. Development of Ranibizumab 72 Affinity maturation (140x) rhu Fab v1 Insertion of murine anti-VEGF-A sequences into a human FAb framework Humanisation Ranibizumab (48 kDa) (E. coli vector to mass produce) Anti-VEGF-A Murine MAb (~150 kDa) Presta, Cancer Res 1997; 57: 4593 Chen, J Mol Biol 1999; 293: 865 63. Properties Molecular weight : 48 kDa Vitreous t1/2 : 9 days Effective retinal