Είναι απαραίτητη η χορήγηση μη στεροειδών αντιφλεγμονωδών παραγόντων σε κάθε χειρουργείο καταρράκτη; Είναι όλα τα ΜΣΑΦ ίδια; Νικόλαος Αρ. Καραμαούνας Οφθαλμίατρος
Is the use of NSAIDs necessary in each cataract operation? Are all NSAIDS the same? Nikolaos Ar. Karamaounas Ophthalmologist
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CME is the most frequent cause of visual decline following modern uncomplicated cataract surgery. It is not a disease itself, rather the endpoint of a variety of processes that lead to the accumulation of fluid in the central retina. It can present with symptoms of blurred or declined central vision, and painless retinal inflammation or swelling. Vision loss is usually temporary, with rare incidences of permanent visual loss.
Cystoid Macular Edema The pathophysiology of CME is not completely understood; however, inflammation due to trauma associated with cataract surgery and a breakdown of the blood-aqueous barrier appears to be at least one of the aspects of the pathogenesis of this postoperative problem.
1. Samiy N, Foster CS. The role of non-steroidal anti-inflammatory drugs in ocular inflammation. Int Ophthalmol Clin 1996; 36: 195-206 14. Flach AJ. Cyclo-oxygenase inhibitors in ophthalmology. Surv Ophthalmol 1992; 36: 259-84
Pseudophakic Cystoid Macular Edema David R. Lally, MD, and Chirag P. Shah, MD, MPH, Boston PUBLISHED 5 MARCH 2014 The natural history of pseudophakic CME is spontaneous resolution of edema with visual improvement in three to 12 months in 80 percent of patients. Only a small proportion of patients will suffer chronic visual morbidity
Incidence of Postoperative CME The incidence of postoperative ME varies depending on the diagnostic technique employed 1,2 : Up to 30% with fluorescein angiogram Up to 41% with optical coherence tomography Clinically significant ME associated with decreased visual acuity after cataract surgery is seen in 2 14% of patients with no risk factors 1,2 Diabetic patients especially those with pre-existing retinopathies are at a higher risk of postoperative ME with an incidence of up to 31 81% 3 1. Grzybowski A et al Clin Interv Aging 2016; 11: 1221-29 2. https://www.reviewofophthalmology.com/article/pseudophakic-cystoid-macular-edema 3. Singh R et al. Clin Ophthalmol. 2012;6:1259 69
The incidence of asymptomatic angiographic CME is much more common than the incidence of symptomatic CME and usually peaks 4 6 weeks postoperatively. CME is considered acute if it lasts <4 months and chronic if it lasts longer.
Preoperative risk factors for CME Pre-existing ocular inflammation, Diabetes mellitus, Ocular or cardiovascular disease, Retinitis pigmentosa, Use of ocular or systemic medications (epinephrine or PG analogues), Previous ocular surgery, and Recent radiation to the head and neck.
Intraoperative risk factors for CME Total phaco energy, Complicated extraction, Capsular rupture, Use of an iris-fixated lens, Ruptured hyaloid face, Iris incarceration, Vitreous loss and Antibiotics in BSS
The longer CME exists, the more permanent damage occurs in the retinal architecture. If you can catch CME early and treat it, you can get a nice resolution of the problem. Once CME becomes chronic, there is permanent damage to the retinal architecture and loss of quality of vision, said Dr. Donnenfeld. OPHTHALMIC PEARLS After Cataract Surgery: Watching for Cystoid Macular Edema Written By: Leslie Burling-Phillips, Contributing Writer
Studies comparing NSAIDs with Corticosteroids Have demonstrated no significant difference in the results between these treatments. However, NSAID treatment appears to be more effective than topical corticosteroids in re-establishing the blood- aqueous barrier, as quantitatively measured by anterior ocular fluorophotometry. Many studies that analysed the effects of NSAIDs on postoperative inflammation included the concurrent administration of corticosteroids, suggesting that NSAIDs and corticosteroids have the potential for synergistic activities. Non-steroidal anti-inflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery. Juthani VV 1, Clearfield E, Chuck RS. Cochrane Database Syst Rev. 2017 Jul 3;7:CD010516. doi: 10.1002/14651858.CD010516.pub2. Shelsta HN, Jampol LM. Pharmacologic therapy of pseudophakic cystoid macular edema: 2010 update. Retina 2011; 31:4 12
Beneficial effects of NSAIDs over corticosteroids stabilization of intraocular pressure, provision of analgesia and reduction of the risk of secondary infections.
The edema has a small but lasting effect, which makes the argument for prevention more compelling, Dr. Roberts said. If ophthalmologists pre-treat patients with nonsteroidal anti-inflammatory drugs (NSAIDs), the inflammatory cascade of prostaglandins is interrupted, which fosters less inflammation and less CME. Dr. Roberts coauthored a study presented at the 2006 Joint AAO/APAO Meeting in November that compared the use of pre- and postop ketorolac plus postop steroid treatment with steroid treatment alone in cataract surgery. When final visual acuity, OCT changes and contrast sensitivity were compared in the two groups, the patients on ketorolac exhibited significantly less retinal thickening and a lower incidence of CME.
NSAIDs indications Maintenance of Mydriasis During Cataract Surgery Pain Management and Control Postoperative Inflammation Following Cataract Surgery Prevention and Treatment of Cystoid Macular Oedema
NSAIDs Efficacy Safety - Side effects Compliance
Side effects temporary stinging or burning in the eyes for 1-2 minutes when applied, eye redness, headache, dry or sticky feeling in the eye, feeling like something is in your eye, itching or watering of the eye, increased sensitivity to light, nausea, vomiting, or stuffy nose
1 st Question To NSAID or NOT to NSAID
Part 2
Currently, 0.1% diclofenac, 0.5% ketorolac, 0.09% bromfenac and 0.1% nepafenac are the only topically applied NSAIDs with FDA and EMA approval for the management of inflammation after cataract surgery
Δραστική Ένδειξη 1 ημέρα πριν Διεγχειρητικά Μετά Δοσολογία Μέρες Χρήσης Νεπαφενάκη Πρόληψη και θεραπεία μετεγχειρητικού άλγους και φλεγμονής που συνδέονται με χειρουργική επέμβαση καταρράκτη Μείωση του κινδύνου ανάπτυξης μετεγχειρητικού οιδήματος ωχράς κηλίδας που συνδέεται με χειρουργική επέμβαση καταρράκτη σε διαβητικούς ασθενείς Ναι Ναι 30-120 λεπτά πριν το χειρουργείο Ναι 1 φορά ημερησίως Έως 60 Αναστολή της εγχειρητικής μύσης κατά τη διάρκεια της εγχείρησης καταρράκτη Μετεγχειρητική φλεγμονή στην εγχείρηση καταρράκτη και άλλες χειρουργικές επεμβάσεις Δικλοφενάκη Προφύλαξη κατά της εμφάνισης κυστεοειδούς οιδήματος της ωχράς κηλίδας που συνδέεται με εξαγωγή φακών καταρράκτη και τοποθέτηση ενδοφθαλμίων φακών Όχι 5 σταγόνες 3 ώρες πριν το χειρουργείο Ναι 3-5 σταγόνες Όσο χρειάζεται Μη επιμολυσμένες φλεγμονώδεις καταστάσεις του προσθίου ημιμορίου του οφθαλμού (π.χ. χρόνια μη επιμολυσμένη επιπεφυκίτις) Φλεγμονή μετά από τραυματισμό: διαμπερείς και μη διαμπερείς κακώσεις Κετορολάκη Πρόληψη και μείωση φλεγμονής μετά από χειρουργείο καταρράκτη 24 ώρες πριν Όχι Ναι 3 φορές ημερησίως 21-28 Βρωμφενάκη Θεραπεία μετεγχειρητικής φλεγμονής μετά από χειρουργείο καταρράκτη Όχι Όχι Ναι (24 ώρες μετά) 2 φορές ημερησίως Έως 14
Nepaphenac as a prodrug After topical ocular administration, nepafenac penetrates the cornea and is converted by ocular hydrolases into amfenac Amfenac, the more active metabolite, is thought to inhibit COX-1 and COX-2, enzymes required for PG production The safety and efficacy of nepafenac have been documented
As a prodrug, nepafenac may provide an added factor of safety to the cornea because less active drug will be present on the cornea
Prodrug advantages Increase permeability through tissues Increase the time of drug action Less adverse effects Enhance drug targeting Better compliance due to their characteristics Better bioavailability
Συγκέντρωση στο Υδατοειδές (ng/ml) Nepafenac provides a reservoir for the formation of the active metabolite Amfenac Ophthalmic bio-availability of Nepafenac was significant higher than Bromfenac and Ketorolac Walters T et al. J Cataract Refract Surg 2007;33:1539 250 200 Nepafenac & Amfenac Nepafenac 150 Amfenac 100 50 Ketorolac Bromfenac Time post-dosing (h) 0 0 0.5 1 2 3 4 Nepafenac + amfenac (n=25) Nepafenac (n=25) Amfenac (n=25) Ketorolac (n=25) Bromfenac (n=25)
Key study endpoints Primary outcome measure The proportion of patients who developed ME ( 30% increase from preoperative baseline CSMT as measured by SD-OCT) within 90 days following cataract surgery Primary outcome measure The proportion of patients with improvements in BCVA of 15 letters from the preoperative baseline to Day 14 and maintained through Day 90 Secondary outcome measure The proportion of subjects with a > 5-letter loss and a >10-letter loss in BCVA from Day 7 to any visit BCVA, best-corrected visual acuity; CSMT, central subfield macular thickness; ME, macular edema; SD-OCT, spectral domain optical coherence tomography 1. Singh RP et al. Ophthalmology. 2017 (Epub ahead of print) 2. https://clinicaltrials.gov/ct2/show/nct01872611
A high percentage of patients completed the study in both the treatment groups Total patients randomised (N=605) Nepafenac 0.3% n=301 Vehicle n=304 Completed study n=277 (92.0%) Completed study n=292 (96.1%) Discontinued study (n=24) AE (n=3) Lost to follow-up (n=8) Physician s decision (n=1) Withdrawal by subject(n=6) Reason not provided (n=6) Discontinued study (n=12) AE, prior to treatment (n=1) AE (n=1) Death (n=1) Death, prior to treatment (n=1) Lost to follow-up (n=1) Withdrawal by subject(n=1) Reason not provided (n=6) AE, adverse event 1. Singh RP et al. Ophthalmology. 2017 (Epub ahead of print) 2. https://clinicaltrials.gov/ct2/show/nct01872611
2 nd Question All NSAIDs are equal?
Μόνο όλα τα γουρούνια έχουν την ίδια σούρλα In Greek because of the difficulty to translate the word sourla to the flat word face Only pigs have same faces
The primary mechanism by which NSAIDs are thought to act in the eye to decrease inflammation is by the reduction of PGs produced by COX within target ocular tissues. The development of a safer alternative to corticosteroids in the treatment of ocular inflammatory diseases is considered a significant advancement in ocular pharmacotherapy. Given the complexity of the inflammatory response, with the involvement of numerous cytokines, numerous cells and the fact that certain compounds are not inhibited by NSAIDs, this group of drugs may still require the concurrent use of corticosteroids to treat postoperative ocular inflammation. Unlike topical corticosteroids, topical NSAID therapy rarely results in serious local or systemic complications. Although there are reports supporting theories of potential pharmacodynamic mechanisms related to NSAID-induced serious corneal damage, these reports should not significantly alter the current favourable benefit-risk ratio of topical ophthalmic NSAIDs when employed in a reasonable and appropriate manner, until clinical evidence dictates otherwise. The development of the prodrug nepafenac is another step forward in achieving higher standards in the safety and efficacy of topical NSAIDs.
Ευχαριστώ πολύ- Thank you Ν. Μιχαλιτσιάνος