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Giảng viên: Tiến sĩ Sashwanthi Mohan, Bác sĩ nhãn khoa, Medcare Eye Centre, United Arab Emirates (UAE)
>> Thank you again to Cybersight for having me. I’m taking on a large topic today called intravitreal injections. Since we’re talking to people all over the world, I’ll keep it as basic as I can and see what we can cover today. Intravitreal injections are drugs through the pars plana directly into the vitreous cavity. It’s highly targeted and bypasses the blood ocular barrier. Maximum therapeutic concentration with minimal side effects. That’s why it’s a useful drug that treats these diseases. So how did this start? The first intravitreal injection was done by Ohm where an air bubble was put in an RD. Then intravitreal penicillin. Peymann had several case reports in 1970 to 1974 and the first intravitreal injection which was approved by the FDA was for CMV retinitis. And now we have plenty of intravitreal anti-VEGF agents. The most common is the anti-vascular endothelial growth factors. The examples are listed here. The newer ones are Brolucizumab and Faricimab. There are steroids that are commonly used. The other things that are antibiotics for [indiscernible] vancomycin et cetera. Antifungals are listed here. Intravitreal variables and chemotherapeutic agents. Like methotrexate and infliximab, which are used for infective uveitis. I won’t talk about these because they are newer. I will cover the techniques and the most common agents. Let’s come to anti-VEG F, the “VEG” means Vascular Endothelial Growth factor responsible for the growth of blood vessels. It can cause new vessel growth and causes leakage and retinal swellings — decreases the leakage and swelling of the retina. Common indications we use this for are wet or neovascular age-related macular degeneration. CRVO or BRVO with the neovascular complications and macular edema associated with them. The diabetic macular edema. Choroidal neovascular membranes due to other causes. Neovascular glaucoma. And we can use it preop for PDR and vitreohemorrhage. Other indications like Eales disease, refractory post-surgery CME. Coats disease and retinopathy of prematurity. It can be used for iris neovascularization. Blood flow keratoplasty and Pteygomim. Contraindications. Fibrovascular proliferation. Active ocular periocular information, uncontrolled hypertension. Cardiovascular disease or recent stroke. Known hypersensitivity to the agents and pregnancy and lactation. Let’s come to the first poll question, what is the first FDA approved anti-VEGF? Most of you seem to have answered Bevacizumab but the first FDA approved was pengaptanib in 2004. And the others are listed here. Bev is not FDA approved. This table gives us an idea about the different anti-VEGFs. I will go through the important points. Lenvatinib is not used much anymore because the other ones have better affinity to VEGF-A. [indiscernible] VEGF in all forms. Ranibizumab attaches to all forms with stronger affinity. The dose is 0.3 mg every six weeks. Ran is given 0.5 mg every four weeks and Alilbercept is 2 mg every four weeks. Ranibizumab is used widely because it has the advantage of being lower coast. Newer anti-VEGFs some still if the phase trials and not FDA approved. The list of them is here on the slide. I just want to talk about two important ones that are FDA approved. The first is Broucizumab. It’s humanized monoclonal single chain variable fragment against VEGF A. Higher molar dosing because of lower molecular weight and a T 1/2 of 3 days. [indiscernible] it has an incidence for these conditions and not FDA approved for retinal vein occlusions. We have to be careful when using it to make sure we know what we are using it for. The other one is Fearicimab. It’s a bi-specific antibody against VEGF A and has more sustained vascular stability and FDA approved for wed AMD and DME. The adverse effects can be ocular or systemic. The most important thing that we need to look at for in these patients endopthalmitis. There is ocular hemorrhage. They can be raised intraocular pressure in glaucoma. They can have cataract formation especially if the — there was a lens [indiscernible] during the intravitreal injection. They can have retinal tears and detachment and intraocular information. And rare are RBON and NAION and corneal melt and retinal toxicity. Systemic side effects are myocardial infection, TIA, deep vein thrombosis, pulmonary embolism and thrombophlebitis. Steroids. We use dexamethasone implant that is used most commonly. We also use the Retisert and there is an implant of [indiscernible]. The indications for steroids are usually pseudophakic CME. Diabetic macular edema. Macular edema associated with vein occlusions. Neovascular AMD and uveitic CME. They are contraindicated in patients with hypersensitivity. Active ocular or periocular infections. Glaucoma patients with cup disk ratio more than 0.8. DEX has to be used with caution with torn posterior capsules or an anti-chamber. Risk of the migration of the implant. This are multiple case reports that show this can migrate to the anterior chamber in patients with these kinds of conditions. Triamcinolone is given by a 27 gauge needle intravitreal. Prolonged duration. Acts as a depot injection when injected into the sequestered cavity. T 1/2 is 18.6 days. Poll question what, what is Ozurdex? (reading the choices). Okay. So again, most of you got A bio degradable 300 mg. But it’s 700 micro gram implant. FDA approved and has extended release in the vitreous cavity. It lasts 3 to 6 months. It can be used in non-infectious uveitis. Off-label use is seen in Ivine Gas Syndrome. Coats disease, radiation maculopathy, et cetera. In this picture you can see a whitish implant material. This is the DEX implant that is injected in this patient. The adverse effects of these steroids are cataract formation. Elevated IOP and glaucoma. And endophthalmitis. Sterile endophthalmitis. It’s not infectious. And DEX implant or other steroid implants have a risk of hypo-Tony. And migration to the anterior chamber. Coming to the third important intravitreal drug. These are antimicrobials. They are listed here. They can be antibacterial or antifungal or antiviral. The most common antibacterial ones are listed here. Antifungal are amphotericin and voriconazole and the antiviral ones are listed here. I want to concentrate or antibacterial and antifungal which are most commonly used. Coming to poll question 3. What are the drugs of choice for acute preoperative Endophthalmitis? (reading the choices). Okay. So most of you got it right. It’s vancomycin and ceftazidime. That’s the most common. Just having a rough idea. Vancomycin works against gram positive and the drug of choice for staph and MRSA. And ceftazidime is gram negative and produces levels greater than 2.25 when injected intravitrealy. Amikacin is not used much because of macular toxicity. And cefazolin are not used. Antifungals, amphotericin B has high affinity for the fungal cell wall and binds to it causing cell death. [indiscernible] helps to inhibit the P450 mediated alpha demethylation which is a step in fungal synthesis. Acts against Fusarium and Candida and yeast and filamentous fungi. Dexamethasone is used when there is severe inflammation. The dosage is 400mcg. Not used in endophthalmitis. It decreases inflammation and has a T half of 3.34 hours. What is the dosing of antis of endophthalmitis for bacterial. They are listed here. Endophthalmitis with severe vitreous information we need to use dexamethasone. Fungal is amphotericin B. And voriconazole. It’s easy to, difficult to remember the doses and we do need to dilute the drugs because they don’t come directly in these doses and they come in separate vials. This table is not easy to remember. It’s not something that we can keep in our memory with us. We have to carry a picture like this along with us so we know exactly how to dilute these drugs. We need to get the correct concentration to inject intravitreal. I recommend that everybody has a picture like this for these drugs. Common adverse effects of endophthalmitis is hemorrhagic occlusive vasculitis and macular toxicity. And gentamicin was used and that causes retinal toxicity and it’s avoided now. In endophthalmitis specifically, I’m taking two or three slides to explain what we do. Given an injection in ophthalmitis is different than other cases. In ophthalmitis, we have to find out what the organism is. We have to do an anterior chamber or vitreous tap prior to injection. When we prepare the injection, we need to give it immediately or as soon as possible. A limbus or pars plana route is according to the phakic status of the patient. We can do the vancomycin separately or combine them together. And we have to do a paracentesis after the injection. Coming to how to do an AC tap. We do topical anesthesia and place a speculum and put in iodine. Usually a 30 gauge needle and enter the anterior chamber parallel to the iris. 6 o’clock. With a tip of the needle at the mid peripheral — after that we inject 0.1 ml. We need to use a cotton tipped applicator where we entered the anterior chamber and give an application of gender pressure for 10 to 20 seconds. We patch the eye and reevaluate after 30 to 60 minutes. We need to look for anti-chamber depth and if there is hyphema or not when we were making the AC tap. The other thing that we can do is a vitreous tap. Outpatient clinic tap and inject procedure. They do a strand adrenal gland preparation. A retro bulbar block and a speculum is placed. And using a 30 gauge butterfly needle with a 10cc syringe, that is what is used. Around 0.2 to 0.5 ml of vitreous is removed by slow suction. A vitreous tap can be done in case of not doing a vitrectomy. It gives us a better analysis. So vitreous tap can be done in an IOP setting. It’s important how do we analyze the samples. We need to send it for gram staining and Giemsa staining and send for culture that takes longer. We can start empirical treatment based on the gram stain of the KOH but we have to wait for the final treatment and antibiotic sensitivity based on the cultures and we can send for PCR for pan fungal genomes. Fungal is usually Sabaroud dextrose agar. Coming to the main thing that I wanted to cover in this is ten tips for intra-vitreal injections. First have the correct diagnosis. We have to make sure that the injection that we are giving for this patient is indicated for this patient and whether they have responded previously. We need to know the history of the patient. We do have to establish a correct diagnose before we go ahead with the injection. That is step one. Step two, prior to treatment with anti-VEGF or other injections, we have to treat active infection. Blocked NLD or any positive regurgitation of the lacrimal sac or active blepharitis should be treated prior to infection. If we go with the anti-VEGF and these things exist, we will end up with ophthalmitis. Pre-injection we need to confirm the name of the patient and the eye that you’re injecting. It’s like a time out. You confirm the indication and type of intravitreal injection. You make sure if you’re giving [indiscernible] for that patient, that patient is receiving the [inaudible]. It’s important to get an informed written consent. You mention the indication, explain the procedure, the risks, explain the other options and when it comes to bevacizumab, it’s off label. Pupil dilation can or cannot be done. It has been recommended that in newer, people giving anti-VEGF for the first time, it’s preferred to do a dilated pupil but it’s not always necessary. Equipment, on the left most of the equipment is present in this picture. You need to use cotton buds. Buds soaked in iodine, a syringe, an 18-gauge needle. And a speculum. A sterile drape, there is no evidence to support use but I prefer to use it. It’s not indicated as long as the eyelashes are away from the injection. Coming to anesthesia. It can be topical or subconjunctival. Topical drops or gel are preferred. That is what I use. Lidocaine can be given using a 27 gauge or 30 gauge needle in the location of the injection. Swabs can be applied to the injection area to give anesthesia before you give the injection in that area. The fifth one, asepsis and disinfection. This is very, very important because endophthalmitis is one of the most common complications. [indiscernible] we have to do hand washing, wear gloves. Wear a mask and minimize talking. There should be less discussion after the patient is on the table because that helps to reduce the contaminants in the room. Povidone iodine is the most important thing for asepsis. 10 percent is used to clean the lashes and lid. And 5 percent is applied to the conjunctival sac and over the ocular surface after the speculum is placed. This decreases bacterial colonization and risk of endophthalmitis. And it’s been proven this is the main thing that helps to decrease the risk of ophthalmitis. 2 to 3 minutes later povidone iodine is used, iodine is painting a sterile speculum used to open the eyes. Povidone 5 percent is the last drop on the eye before the injection. The speculum helps retracts the eyelids. It’s very important to keep the eyelashes away from the needle tip and area of injection. You can do this by taping the eyelashes in certain patients. I’m showing a video of how the cleaning should be done. This is with povidone iodine 10 percent. Multiple sweeps across the eye and the entire eye should be cleaned with the povidone iodine. And the surrounding area should also be cleaned up after you clean the eye. Then use a povidone iodine 5 percent to clean the conjunctival sac. Keep the eye open. If you repeat the anesthetic, you have to repeat the povidone before you start the injection. This video shows how to drape in a patient. Although there have been the latest recommendations do not recommend sterile draping, I prefer draping the patient because it does give us a better way of retracting the eyelashes. You can see that a sterile drape is being used and placed over the eye of the patient. By retracting the eyelids up and down. And then the sterile drape is opened. Sterile drape is now covering the eye. And now you can see it’s covering the eye. We can use a scissors to open up the area, cut the area and make an opening. Then we can use an eyelid speculum to retract the eyelids. You can see here the eyelid speculum is used to retract the eyelids and the eyelids are away from the ocular surface. Draping helps prevent the eyelashes from coming onto the ocular surface. To minimize the risk factors are eyelid speculum and lid retraction, povidone iodine. Face mask and no talking. Hand washing and drugs. Prefilled syringes have a lesser risk of ophthalmitis. And when doing bilateral injections, we need to treat each eye separately with separate instruments and separate lot numbers for each medication. The last poll question, what is the site of injection of intravitreal agents? That’s right. Most of you got it right. The pars plana. We need to know the anatomy of the eye to understand where we have to inject. It’s very important to know this. The injection site is usually the pars plana. It avoids lens damage and retinal breaks and vitreous base damage. It can vary in anti-posterior diameter and nasally it’s 3 mm wide and temporally it’s wider. And also the lens zonules inserted into the ciliary body avoiding the pars plana is a good way. Based on the age and the lens status, the distance from the injection will vary. In babies and infants the eye is smaller. Anti-ly placed pars plana and a relatively greater size of the crystal lens. We have to give the injection closer to the limbus. One to six months of age, it’s 1.5 mm from the limb pus. Six months to one year, 2 mm. One to two years, 2.5 mm. And two to six years it’s 3 mm. At 7 years it reaches adult side. We have to decide based on the phakic state of the patient. We have to give 4 mm from the limbus. In a pseudophakic patient it’s 3.5. And aphakic it’s 3 mm from the limbus. The technique. We need to know the needle characteristics, the injection volume and site and depth and angle of the needle insertion. The needle should be usually smaller than 25 gauge. And 30 gauge is the most commonly used. Here is a 30 gauge one. 27 gauge is used only for triamcinolone because they are larger crystal molecules. Larger needles are more traumatic and cause vitreous reflex and hemorrhage. The injection volume is 0.05 ml. That is how much we give. The maximum safe volume to inject without pre-injection is only 0.1 to 0.2 ml. The injection site, any quadrant can be chosen. The patient is asked to look opposite to the quadrant chosen and distance to the limbus is based on the age and phakic status. This is a 4 mm you can see an indent here where the calipers are pressed to the sclera. The injection is directed to that point. Coming to the depth and angle of the needle insertion, the depth is 5 to 7 mm. Perpendicular or oblique. Retracted to prevent scleral and conjunctival opening overlap. Injected into the vitreous. A sterile cotton swab is placed over the injection site to prevent reflux. You can see the indent is there and the injection is being entered on a site 4 mm in the limbus and towards the vitreous cavity. And then the injection is slowly injected into the mid vitreous cavity. So the injection has taken place. And the injection is removed again, the needle is removed in the same pathway that it entered. A bud is used immediately as you’re withdrawing the needle so there is no reflex at that site. This is how you do any kind of injection. The DEX implant is slightly different. This is showing a small video to show you how to do it. We enter more obliquely with the bevel facing towards the eye and make it more perpendicular. Unfortunately this video is not seen very well. This actuator here that you can see in the top right picture, that should be pressed flush against the applicator and only intravitreal. And after you withdraw, you have to place a cotton swab there because there will be reflex. I want to show the video again. Enter obliquely and perpendicular. And press the actuator so it’s flush against the applicator and implant. And then press the bud at the site of the needle insertion. A specific consideration is for ROP babies. The distance is 0.75 to 1 mm from the limbus. The angle is parallel to the visual axis to avoid lens touch. The length is 32 gauge thin walled 4 mm stainless steel needle or a 30 gauge 0.5-inch needle where one-third of the needle is inserted into the eye. These are the precautions you have to make in premature ROP babies. Point No. 8 is most injection. What do you do immediately post injection: You need to check the IOP digitally. Routine paracentesis is not recommended. Ask the patient if you can see light or count fingers. This is checking vision in a gross way. Use indirect ophthalmoscope to look for central artery pulsations to determine the IOP. The eye, instill 5 percent povidone iodine when closing the eye and it can be patched for 1 to 2 hours. Preoperative precautions. Maintain lid and eye hygiene. Avoid head bath for 4 days. Follow up instructions. And patient needs to review in case of pain or decreased vision and other symptoms. Topical antibiotics whether they need to be given or not is controversial. I do give it. But whether they help or not is not routinely recommended for all patients. Final thing is the follow up. One of the main follow ups is for IOP check up. This is needed in steroid injections where there can be intraocular pressure spike. And the follow up depends on the disease being treated and duration of treatment. Whether it’s the first time the patient is being treated or [indiscernible] basis treatment, the follow up should be based on all this. Usually, between 4 to 6 weeks. In antimicrobial injections, it’s more frequent follow up. 48 to 72 hours to evaluate the status of the endophthalmitis and looking at the fundus and see if they are worsening or improving or if they require injections or vitrectomy. Look for treatment effect. Based on the indication if it’s a diabetic macro edema, look for the thickness to see if there is resolution of the fluid. And whether the patient is responding to the particular injection or not. Another important thing is know what complications can happen and manage them. We have to look out for the complications that I managed before. Especially endophthalmitis and increase in pressure, retinal detachment. These complications we have to anticipate and we have to manage them accordingly. I just wanted to give a small point, this is my last slide. A SAFER protocol for ROP babies. S stands for short needle. A is antiseptic or antibiotic. F is follow up. That is 48 to 72 hours post injection. We need to follow up earlier for the ROP babies to see how the vascularization of the retina is. E is attention to detail. Clean environment. And R is recheck. That is one to two weeks following the injection and until the full vascularization of the retina or whether the baby requires additional laser, we have to keep rechecking. This is a nice mnemonic to remember. We have to establish the correct diagnosis. Treat active infection. Follow all the pre-injection protocols. Confirming the eye of the patient, the name of the patient, confirming the indication. Informed consent. And pupillary dilation, yes or no based on the surgeon’s preference. All the equipment should be sterile and available. We shouldn’t be going in search of any of the equipment and everything should be available. Asepsis and disinfection is one of the most important steps. Povidone iodine is known to decrease infection. It’s absolutely necessary for prevention of ends ophthalmitis in intravitreal injections. The other important thing is eyelid retraction. The eyelashes should not come into the field or touching the field. Knowing the age of the patient and the technique and how much you will inject and the size of the needle and the angle of the needle and depth is important. And immediate postop precautions. And giving proper postop precautions to the patient and following up the patient in the appropriate time to look for treatment effect and rule out any complications. That’s all for today. It is a large topic and I’m not able to cover everything that was asked for. This can be each drug can be a separate topic all together. Hopefully this was useful. If anybody has more questions, they can contact me on LinkedIn or via email. Thank you so much. >> Thank you, Dr. Mohan. We have about 13 questions so far if you want to open up the Q&A. >> How long do you usually wait before injecting anti-VEGF after CV or stroke? Six months. We have to get clearance from the cardiologist. If the patient is stable we can go with the anti-VEGF injection. If the patient is suitable for steroid injections, pseudo-phakia and does not have preexisting — we can go ahead with the steroids and anti-VEGF also. The next question, what is the opinion of pain injection in the setting of intravitreal injections. I don’t recommend pre-injection para cent tee sis. The maximum is 0.1 ml. We will not require AC paracentesis at all. It’s not recommended. In cases where the vitreous tap and antibiotic injection, do you use the same entry point? Not necessarily. Instead of making a bigger wound, it’s better to use two different entry points. Depends on the needle you’re using. You can use the same entry point and give it as well. Maximum volume. 0.1 to 0.2 ml. What is your opinion about simultaneous bilateral injection. I do not prefer it unless the patient is aged and is not able to come often. You have to treat each eye separately. It’s better to get completely different set of instruments and different — even the batch number should be different so that there is no risk of endophthalmitis in both eyes because of the bilateral injection. Is it safe to give intravitreal dexamethasone with an etiology unknown. No, it’s not. Bacterial endophthalmitis especially with a vegetative matter or wood or anything, it’s not a good idea to give it. Bacterial endophthalmitis, better to confirm it and reduce the information and we prefer to give it in those patients. Any advantage of is there any advantage of the oblique injection technique over the perpendicular way? Oblique injection technique has lesser leakage. Perpendicular will not create a — path. It’s similar to how you make a cataract incision. Both ways are okay because it is a very tiny gauge needle that we’re using. The main reason no head wash is not to allow contaminants in. It’s just to avoid anything unnecessary going into the eye. Advantage and risk to superior and inferior injection site. Superior is better. Superior, I mean I don’t know if there is evidence. I’m not sure about that. But actually, I feel inferior is easier because of patients, everybody has a [inaudible] phenomenon where the eye goes up. They have lesser tendency to move the eye when it’s up. You can give an inferior injection at that time. But supra temporal is also a good option if the patient is able to look down properly. Is it indicated to give intravitreal injection in a sterile or clean room? A lot of people give it in — settings also. But there should be some sterility involved. Not just off the table. At least the tray, sterile tray and everything — has to be sterile. But there are lot of people that do it in OPDs but I give it in the sterile injection room. What is the safest anti-VEGF for a one-eyed patient? There is no such thing as safest. It depends on the indication. I don’t think there is a safe anti-VEGF but with a retinal vein occlusion I would not give (inaudible). If you’re talking about a non-center involving the macular edema, you can use a laser. Sometimes [indiscernible] macular edema if it’s good vision and a small cyst, you can try NSAIDs. But there is no alternative. It depends on the indication. You see patients routinely obtain injections. Depending on the injection, I like to see them after a couple of days. For intravitreal anti-VEGF on day one and three to four weeks later. What is your opinion about triamcinolone. It’s cheaper. It’s cheaper than the DEX. But DEX is more appropriate for CME patients if they’re pseudophakic or nonresponsive to anti-VEGF or have prognostic markers of OCT that say that steroids should be used instead. As a point of injection, the conjunctiva and sclera is the same or different lengths? They should be different lengths. Retract the sclera and give the injection so when it goes back it covers the scleral opening. Change injection site in case of frequent injections? Yes. It’s preferable. When you are doing frequent, like maybe half a millimeter from each other. We don’t want the same site to become bigger and bigger. If you can see where the previous injection was given, you can give it slightly away from that. Safest anti-VEGF in ROP. [indiscernible] is used and — used in some studies. Do you inject anti-VEGF if they have high blood sugar on the day of injection? No. I would prefer not to inject on the same day. It causes increased organism contamination. So there is a risk of endophthalmitis in that situation. I prefer to wait. High blood sugar depends on the patient. We have to make a called based on that, also. How do you prevent subconjunctival hemorrhage at the site of injection. When you’re looking through the microscope, avoid a blood vessel. When you hit a blood vessel, that is when you will be causing a hemorrhage. You have to give the injection in an area that is less vascularity. That’s the way to avoid subconjunctival hemorrhage. Do we give two antibiotics together? No. Vancomycin is separate and ceftazidime is separate. Vancomycin has to be given separately. Pupil dilation before injecting anti-VEGF. Before is not as important as it is after. After it’s used through the ophthalmoscope and make sure the central artery pulsations and IOP is fine. And in DEX implant, you can see the implant is there. Before, why is it important before dilation? To confirm that you have the right indication. I prefer to dilate the patient and have a look before injecting anti-VEGF. This question is already answered. Some questions are getting repeated so I’m just going. Why the site of injection different in ROP. They are smaller eyes and they have immature pars plana. And they have a larger crystal line lens. If you don’t go a little anterior, we will cause a lens touch. That is why it’s 0.75 to 1 mm behind the limbus. Can we do intravitreal injection without a microscope? I sometimes use the ophthalmoscope along with a — lens to get a magnified view. Or a loop. You can do it without a microscope but you have to use something to magnify the area you’re giving it to avoid the blood vessels. When administering anti-VEGF how do we prevent [indiscernible] in a phakic eye. Make sure the measurement from the limbus is exactly 4 mm and direct the needle towards the mid vitreous cavity. It should come anterior and directed towards the mid vitreous and 4 mm from the limbus. Any other questions? What should we do in case of a dry tap? You treat based on the findings. You have to give vancomycin and ceftazidime and keep following up with the patient and keep examining the fundus or doing a scan and see if there is improvement. You repeat the injection if there is no improvement. How do you follow up a macular edema patient that you give bevacizumab. You have to give loading doses one month apart. Look for the effect of treatment. Look at the biomarkers. A lot of OCT biomarkers show that we need to use an intravitreal anti-VEGF or a steroid. Follow up with the biomarkers and see if the patient is improving after three doses or not. If not, you might have to change the anti-VEGF or change to a steroid. Systemic control is important.. Injecting 0.05 ml is the ideal. You can go ahead and inject that. There is no difference in effectiveness of drugs because of that. How many intravitreal injections will you do in endophthalmitis. It depends. Each patient is different. You might have to take up a — what about the bleeding profile before injection? I don’t follow that. But in patient who is are on aspirin or anything, you can get a bleeding profile done. Or warn the patient there is a good risk of subconjunctival hemorrhage because they’re prone to bleeding episodes. Divide the vial between two patients. Only one for Lucentis. Must we do AC paracentesis — no. We don’t need to do either of these in ROP. What’s the purpose of dilated pupil? I explained that: How long to wait since applying iodine 10 percent to the next step. Give it 2 to 3 minutes. Once you put the drops, give it a minute or so before you go to the next step. How long do we give intravitreal anti-VEGF. If it’s to regress a neovascularization, you give one and see if it regresses. If it’s resolving, you can observe. If not, you might have to go with [indiscernible]. What are the roles of ophthalmic intravitreal injection. To set up the sterile tray and help in the draping and retracting the eyelid speculum. It’s important to maintain sterility and confirm the patient and make sure we’re doing the correct eye. That is the roles of the assistant during the injection. After IV injection, it’s possible, yes. The mechanism is supposed to be because posterior vitreous detachment is induced. Especially in people who do not have a preexisting ME and this can lead to retinal detachment. That is why it’s important to know the complications and do a full retinal examination and peripheral examination on follow up in these patients. Explain they do have to come if they see flashes or floaters. I think most of it has been covered either in the presentation or in my answers. Is an anti-VEGF selection method for AME versus DME. They’re all FDA approved so you can start with any drug and change it accordingly. If the patient wants a longer follow up, you can choose another drug. There is no selection method for the treatment. But if someone didn’t respond, you would have to switch anti-VEGFs in that case. What’s the limit of BP and FP? I don’t think there is a particular protocol for that. I would say at least if it’s anything above 120, 130, I would not give anti-VEGF in BP above 150 or 100 on that day. How long to hold anticoagulant. You don’t need to do that before injections. Can fasting and PP limit? That’s what I said. There is no proper protocol for this. But anything above 130 to 140 for fasting and maybe more than 250 for postprandial, I think it’s better to avoid injections on that day. Office based injections. You mean in the OPD setting. Of course, a lot of people are doing it. It does not seem to be an issue as long as the sterility and disinfection methods are followed. It’s a good idea to have a sterile injection room because they are at high risk of anything going into the eye and high risk of endophthalmitis. Do you — the vial of anti-VEGF before use? It’s not done. We will be drawing the injection with the 18 gauge needle from this one without touching the vial of the anti-VEGF. Pilocarpine to close the angles to reduce the risk of IOP. I have noted done this. I don’t have a personal opinion of this. To reduce the risk of raised IOP. You mean in patients with previous closed angles. I have not do this. Sorry, I can’t answer that question. Macular edema, you can try. But some cases will require surgery in the end. There are many cases where the CME can resolve with intravitreal injection itself. Do you use — for naive patient? Yes. If it’s a patient who is pseudophakic. You can try, especially in the patient does not want to come for monthly follow ups. That is important. If the patient doesn’t want to come for monthly follow up, DEX has a longer duration of action, 3 months before you need to repeat it again. Ideally, depending on the indication, anti-VEGF is the first choice with ARMD or DME. But you can do it for an [inaudible] patient. A patient already has peripheral changes and indication for anti-VEGF. If they have a retinal break, definitely you have to laser before you do anti-VEGF. No doubt about it. There was a recent article published where the recommendations are given. There is no proper consensus about this. If the patient can — the injection, it’s preferable to treat anything which pre-disposes to retinal detachment. Like degeneration or retinal break, these have to be treated before we do the intravitreal anti-VEGF. >> Thank you so much. Thank you.