Sindrome di Irvine Gass

Presentazione sul tema: "Sindrome di Irvine Gass"— Transcript della presentazione:

1 Sindrome di Irvine Gass
Università degli Studi di Foggia Dipartimento di Scienze Mediche e Chirurgiche Cattedra di Oftalmologia Direttore: Prof. Nicola Delle Noci Sindrome di Irvine Gass C.Iaculli

2 SINDROME DI IRVINE-GASS
Edema maculare cistoide post chirurgico descritto inizialmente da Irvine (1953) e dimostrato fluorangiograficamente da Gass e Norton (1966 )

3 4/25/2017 Burden del CME Principale causa di riduzione visiva post-cataratta non complicata1 Incidenza 0.1–2.35%,2 ICCE > ECCE > Faco3 Maggiore incidenza (3.05%) in pazienti con diabete mellito4 La maggior parte dei casi si risolve spontaneamente in mesi dopo la chirurgia 1,5 Solo 1–3% persiste6 Tuttavia molto comune per il numero elevato di cataratte 7 Malgrado il miglioramento delle tecniche chirurgiche e nella prevenzione, il trattamento rimane ancora dibattuto1 1. Loewenstein A & Zur D. Dev Ophthalmol 2010;47: Henderson BA et al. J Cataract Refract Surg 2007;33: Flach AJ. Trans Am Ophthalmol Soc 1998;96:557 4. Schmier JK et al. Retina 2007;27:621 5. Lobo C. Ophthalmologica 2012;227:61 6. Soloman LC. J Cataract Refract Surg 1995;21:73 7. Ray S & Amico DJ. Semin Ophthalmol 2002;17:167

4 Etiopatogenesi Etiopatogenesi incerta
Alterazione del microambiente dopo la chirurgia 1 Trazione Vitreo-maculare2 Ipotonia Oculare6 Danno fototossico6 Infiammazione 3,4 Generalmente accettata come fattore scatenante 5 1. Hruby K. Klin Monatsbl Augenheilkd 1985;187: Tolentino FI & Schepens CL. Arch Ophthalmol 1965;74: Rossetti L & Autelitano A. Opin Ophthalmol 2000;11:65 4. Miyake K & Ibaraki N. Surv Ophthalmol 2002;47(Suppl1):S207 5. Lobo C. Ophthalmologica 2012;227:61 6 Flach AJ. Trans Am Ophthalmol Soc 1998;96:

5 Barriera emato-retinica interna Barriera emato-retinica esterna
Etiopatogenesi infiammazione intra-oculare secondaria al trauma chirurgico rilascio di PG rottura della barriera emato-oftalmica passaggio di fluido nello spazio sub-foveale Barriera emato-retinica interna Barriera emato-acqueo Barriera emato-retinica esterna Hyung et al., Etiology and treatment of the inflammatory causes of cystoid macular edema Journal of Inflammation Research 2009:2 37–43

6 PREDISPOSIZIONE DELLA REGIONE MACULARE ALLO SVILUPPO DELL’ EDEMA
Anatomia Densità cellulare Densità vascolare Fibre di Henle Assenza cell di Muller Spazio extra-vascolare Tessuto ad elevato metabolismo aerobio

7 Classificazione CME stage Description Angiographic CME (9-19%)
(60% ICCE, 20% ECCE) Presence of fluorescein leakage in FA Classified into 4 levels Mostly asymptomatic Clinical CME (<3%) Presents with decreased vision (≤20/40 BCVA) Diagnosed by biomicroscopy OCT CME (41%)2 With or without symptoms or visual loss the presence or absence of CME can be described in 3 ways: angiographic examination, clinical examina- tion, and the presence of retinal cysts or increased thickness or volume as measured by optical coherence tomography (OCT) The measured incidence of CME varies with these three techniques (OCT is the most sensitive way to detect CME, followed by angiogra- phy, and clinical examination is the least sensitive). 1. Loewenstein A & Zur D. Dev Ophthalmol 2010;47: Lobo CLet al. j Cataract Refract Surg 2004;30:

8 Classificazione CME classification Definition Acute
Appears within 4 months of surgery Late onset Occurs after >4 months post surgery Chronic Lasts >6 months Recurrent the presence or absence of CME can be described in 3 ways: angiographic examination, clinical examina- tion, and the presence of retinal cysts or increased thickness or volume as measured by optical coherence tomography (OCT) The measured incidence of CME varies with these three techniques (OCT is the most sensitive way to detect CME, followed by angiogra- phy, and clinical examination is the least sensitive). Loewenstein A & Zur D. Dev Ophthalmol 2010;47:148

9 Fattori di Rischio Numerosi fattori possono aumentare il rischio di sviluppare un edema maculare post-chirurgico 1 Fattori sistemici  diabete mellito,2 ipertensione Condizioni oculari preesistenti  uveiti, occlusioni venose, DR Complicanze chirurgiche  rottura CP(11.5%-20%), ritenzione frammenti di cristallino (29%), perdita di vitreo, incarceramento irideo 1. Loewenstein A & Zur D. Dev Ophthalmol 2010;47: Schmier JK et al. Retina 2007;27:621

10 Prevenzione Identificazione e riduzione dei fattori di rischio
Valutazione preoperatoria1,2 Stretto monitoraggio post-operatorio Fattori di rischio sistemici / anatomici Precedente chirurgia in occhio controlaterale 1. Lobo C. Ophthalmologica 2012;227:61 2. Loewenstein A & Zur D. Dev Ophthalmol 2010;47:148

11 Prevenzione La profilassi medica può essere di ausilio1,2
Gli Anti-inflammatori possono minimizzare l’edema maculare post-chirurgico3 Studio randomizzato su 60 pazienti sottoposti a facoemulsificazione : volume maculare medio dopo chirurgia 3 clinicians may favor the use of NSAIDs over corticosteroids in some patients given the latter drug’s side effect profile, including high intraocular pressure, wound healing problems, and recurrences after its disuse 1. Lobo C. Ophthalmologica 2012;227:61 2. Loewenstein A & Zur D. Dev Ophthalmol 2010;47:148 3. Cervantes-Costes G et al. Clin Ophthalmol 2009;3:219

12 NSAIDs L’mpiego pre-operatorio di NSAIDs sembra ridurre l’incidenza dell’ CME clinicamente significativo. Ruolo nella prevenzione del CME in pazienti “a rischio” (RD, uveiti) Vantaggi intraoperatori Rossetti L et al. Medical prophylaxis and treatment of cystoid macular edema after cataract surgery. The results of a meta-analysis. Ophthalmology 1998; 105: Shimura, et al. Diclofenac prevents an early event of macular thickening after cataract surgery in patients with diabetes. J Ocul Pharmacol Ther June 2007; 23(3):

13 Remissione spontanea nel 70% dei casi
TRATTAMENTO Remissione spontanea nel 70% dei casi Anti-infiammatori non steroidei (NSAID) Corticosteroidi Anti-VEGF Terapia chirurgica

14 Phospholipids cell membrane
Trattamento Corticosteroidi e anti-inflammatori non-steroidei (NSAIDs) agiscono sulle PG con differenti meccanismi La somministrazione topica mostra maggiori vantaggi rispetto a quella sistemica ( migliore penetrazione)1 Leukotrienes Lipooxygenase Tromboxane A2 Corticosteriods and NSAIDs are used because they suppress prostaglandin-induced inflammation (via distinct mechanisms) In response to various stimuli, cell membrane lipids are converted into arachidonic acid by the enzyme phospholipase A2. Further catalyzation by cyclooxygenase (COX) yields prosta- glandin-type mediators (endoperoxides). Corticoste- roids inhibit prostaglandin synthesis by inhibiting the enzyme phospholipase A2. Whereas, aspirin and various NSAIDs (indomethacin, etc) inhibit prosta- glandin synthesis by inhibiting the enzyme COX further along in the pathway.1 Topical application of NSAIDs does provide adequate drug concentration to suppress prostaglandin synthesis in the anterior segment; however, it may not necessarily lead to sufficient concentration in the posterior segment. It is unclear if the drug has to reach the retina or whether the prostaglandins may be synthesized elsewhere (i.e., anterior uvea). As described earlier, NSAIDs reduce prostaglandin levels by the inhibition of cyclooxyge- nase. Of the 2 main isoforms of cyclooxygenase, COX-1 and COX-2, the latter may have an important role in inflammatory disease processes specifically in the retina where COX-2 is the predominant isoform present in human retinal pigment epithelial cells and found to be increased in inflammatory states.34 Because prostaglandins may be important in inducing VEGF,35 Prosta- glandin E2 production is regulated via cyclooxygenase enzymes— cyclooxygenase-1isaubiquitousprotein important to physiologic housekeeping functions, whereas cyclooxygenase-2 is an inducible enzyme primarily responsible for increased prostaglandin pro- duction during inflammation.20 Newer (but expensive) topical NSAIDs such as bromfenac and nepafenac claim enhanced penetration to the posterior segment. However, the research reaching this conclusion was undertaken largely in animals.57–59 recurrences are all too common when corticosteroids wear off. The long-term benefit of corticosteroids is thus uncertain. Phospholipids cell membrane Phospholipase A2 Arachidonic acid Cyclooxygenase Prostaglandins (PGE2, PGF2, PGD2) Corticosteroids NSAIDs Prostacyclin PGl2 1. Loewenstein A & Zur D. Dev Ophthalmol 2010;47:148

15 NSAIDs Spesso la prima opzione terapeutica nel trattamento del CME
Controverso ruolo nel trattamento del CME acuto (difficile distinguere la risoluzione spontanea dall’effetto dei NSAIDs) Migliori risultati nel trattamento del CME cronico Flach AJ. The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery. Trans Am Ophthalmol Soc 1998;96:557–634. Sivaprasad S, et al. Non-steroidal antiinflammatory agents for treating cystoid macular oedema following cataract surgery: a systematic review. Br J Ophthalmol 2005 Nov; 89(11):

16 VA=02 VA=0.3 VA=09

17 CORTISTEROIDI Inibiscono i mediatori infiammatori ed i fattori di permeabilità vascolare (fosfolipasi/COX) Rallentano la perdita delle Tight junction endoteliali Possibile incremento della IOP Nauck M, et al. Corticosteroids inhibit the expression of vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol. 1998;341:309–315. Antonetti DA, et al. Hydrocortisone decreases retinal endothelial cell water and solute flux conincident with increased content and decreased phosphorylation of occluding. J Neurochem. 2002;80:667–677.

18 CORTICOSTEROIDI Topici Sotto-Tenoniani Intravitreali

19 CORTICOSTEROIDI TOPICI
Ruolo effettivo sul miglioramento del CME ? Diversi studi hanno evidenziato l’effetto sinergico della terapia combinata CORTICOSTEROIDI/NSAIDs Heier JS, et al. Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology. 2000;107:2034–2039. Wolf EJ, et al. Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac. J Cataract Refract Surg. 2007;33(9):1546–1549.

20 CORTICOSTEROIDI per via SOTTO-TENONIANA
Nei casi di CME post-chirurgico resistenti Più alte concentrazioni maculari di corticosteroidi Il confronto tra iniezione sotto-tenoniana di triamcinolone + prednisolone topico vs prednisolone topico mostra migliori risultati (CMT e BCVA), statisticamente significativi, nel primo gruppo, ad un mese dall’intervento. Johnson MW. Etiology and treatment of macular edema. Am J Ophthalmol. 2009;147(1):11–21. Kim SY, et al. Effect of a single intraoperative sub-tenon injection of triamcinolone acetonide on the progression of diabetic retinopathy and visual outcomes after cataract surgery. J Cataract Refract Surg 2008; 34:

21 CORTICOSTEROIDI INTRAVITREALI
Nei casi di CME resistente a terapia topica o di CME cronico Più elevate e durature concentrazioni di farmaco in camera vitrea, grazie anche ai dispositivi a rilascio prolungato Maggior rischio di complicanze (incremento IOP, cataratta, endoftalmiti)

22 CORTICOSTEROIDI INTRAVITREALI
TRIAMCINOLONE ACETONIDE FLUOCINOLONE ACETONIDE (dispositivo a rilascio prolungato) DESAMETASONE (dispositivo a rilascio prolungato) Jonas JB. Intravitreal triamcinolone acetonide: a change in a paradigm. Ophthalmic Res. 2006;38:218–245. Jaffe GJ, et al. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical stud. Ophthalmology. 2006;113:1020–1027. Williams GA, et al. Dexamethasone posterior-segment delivery system in the treatment of macular edema resulting from uveitis or Irvine–Gass syndrome. Am J Ophthalmol. 2009;147(6):1048–1054.

23 TRIAMCINOLONE Boscia: emc di lunga durata ( cronico ) risultati statisticamente significativi a 2 mesi ma non a 11 efficacia a breve termine ma non a lungo termine. Sottolineare la cronicita’ dell’emc Koutsandrea : anche in questo caso emc cronico. Al FU di 12 mesi abbiamo una interessante dissociazione tra acuità visiva e edema maculare con aumento dello spessore centrale e persistenza di un buon risultato visivo e di una buona risposta elettroretinografica multifocale Kostantopulos : emc di durata inferiore abbiamo risulato visivo significativo al fu di 6 mesi . Il 15% dei pazienti comunque non risponde alla terapia e presenta un peggioramento dell’AV . Quindi considerare altre terapie come Desametasone EMC resistente a terapia convenzionale di durata differente AV differente!! Dissociazione tra risultato funzionale e morfologico

24 Triamcinolone Autorizzazione AIFA
Corticosteroide di sintesi fluoro alla posizione 9 che ne aumenta le proprietà anti-infiammatorie Kenalog: off label contiene alcool benzilico altamente tossico per EP Triesence e Trivaris : preservative free granulometria piu’ omogenea approvati dalla Fda per edema in corso di uveiti ( distinguere tra FDA-EMA-AIFA ) Taioftal sospensione acquosa con granulometria <40micron rispetto a<10 del Vitreal S per favorire una maggiore permanenza del farmaco ed un effetto terapeutico Dosaggio preferito per buon rapporto rischi/benefici 4mg Si sta sviluppando un preparato iniettabile che tende a ad assumere una forma sferica e a rilasciare ta in un tempo prolungato Autorizzazione AIFA

25 Desametasone Intravitreale
Proposto da molti Autori come farmaco di prima linea per il trattamento dell’EMC postchirurgico refrattario Vantaggioso rispetto a somministrazione sub-tenoniana Maggiori concentrazioni intravitreali Rilascio prolungato Attività anti-infiammatoria sei volte maggiore rispetto a triamcinolone

26 Desametasone Intravitreale

27 Desametasone Intravitreale
EPISODIC STUDY 50 pazienti arruolati con CME refrattario 61% >15 lettere Riduzione CSMT (302) al secondo mese Picco della IOP al primo mese 49% hanno ricevuto una seconda iniezione entro 12 mesi In >50% nessuna recidiva Bellocq D Br J Ophthalmol 2015

28 Anti-VEGF Il VEGF è implicato nell’aumento della permeabilità vascolare e nello sviluppo di EMC di varia origine L’uso di anti-VEGF si è dimostrato efficace in pazienti con EMC resistente alle terapie mediche convenzionali Efficacia a volte limitata nel tempo. Assenza di trials controllati In pazienti resistenti/non elegibili al corticosteroide IV

29 Anti-VEGF J Ophthalmic Vis Res 2012;

30 Anti-VEGF J Ophthalmic Vis Res 2012;

31 Anti-VEGF

32 TERAPIA CHIRURGICA Fallimento di terapia topica e locale
Incarceramento di vitreo nella ferita chirurgica o presenza di vitreo a livello del segmento anteriore Residui di cristallino in camera vitrea Trazione vitreo-maculare

33 ALGORITMO DI TRATTAMENTO
Topical NSAID + topical corticosteroid Periocular corticosteroid Intravitreal corticosteroid Possibly combined with an anti-VEGF agent or with topical NSAID3 If no improvement in vision is noted after 4 weeks to 6 weeks, Warren et al82 showed that there may be a role for topical NSAIDs in potentiating the effect of combined intravitreal corticosteroid and anti-VEGF injections for the treatment of chronic PCME. Because pseudophakic CME is quite common and is usually self-limited, the authors do not support the use of an expensive newer drug (i.e., topical NSAID such as nepafenac) for the routine prophylaxis of PCME. Less-expensive NSAIDs or corticosteroids may be worth the cost for prophylaxis in higher risk patients, but this remains to be proven in the long term. Pseudophakic CME affecting the patient’s vision at the 2-month to 3-month postoperative period should be treated. If vitreous incarceration, consider surgery If persistent inflammatory reaction, consider IOL removal and/or vitrectomy Loewenstein A & Zur D. Dev Opthalmol 2010;47:148 Shelsta HN, et al. Retina 2011;31:4-12 3. Warren KA, et al. Retina 2010;30:

34 Conclusioni Incidenza ridotta ma impatto notevole
Possibilità di diversi trattamenti ma assenza di consenso Quasi tutti I trattamenti discussi sono off label Necessità di trials randomizzati e linee-guida

35

36

37 Trattamento Carbonic anhydrase inhibitors (acetazolamide)1
Stimulate RPE to pump out excess fluid from the macula May reduce edematous component Case reports demonstrate promising results,2 but no RCT Antiangiogenic agents are a proposed alternative approach in refractory cases VEGF has been implicated in the development of inflammatory ME because it disrupts the BRB Bevacizumab has shown conflicting results 3,4 Ranibizumab has not yet been tested in CME Carbonic anhydrase is present on the apical and basal surfaces of the RPE cell. VEGF has been implicated in the development of inflammatory ME because it disrupts the BRB and increases vascular permeability.13,70,7 The mechanism for bevacizumab-induced reduction of CME may be associated with a downregulation of many cytokines and VEGF combined with conformational changes in the tight junctions of retinal vascular endothelial cell and decrease of vascular permeability.11 A more recent interventional, retrospective, multi- center study73 concluded that intravitreal bevacizumab (Avastin) is a well-tolerated and effective treatment for patients with refractory PCME. Thirty-six eyes of 31 patients with refractory PCME were treated with at least 1 intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab. At 12 months, 26 eyes (72.2%) showed improvement in best-corrected visual acuity, and OCT data demonstrated a statisti- cally significant (P , ) reduction in the mean central macular thickness from mm to mm. 1. Lobo C. Ophthalmologica 2012;227:61 2. Catier A et al. J Fr Ophthalmol 2005;28:1027 3. Spitzer MS et al. J Cataract Refract Surg 2008;34:70 4. Arevalo JF et al. Ophthalmology 2009;116:

38 Other techniques Laser treatment (vitreolysis)
Complications may occur (increase in IOP, retinal detachment)1 Surgical treatment (vitrectomy)2 Patients with chronic ACME because of vitreous adherence to the wound and pupil distortion 6 Or in special cases (i.e. lower and long-standing decreased vision, unresponsive to medical treatment)7 Intraocular steroid implants3 Allows sustained delivery of treatment Implants with fluocinolone acetonide and dexamethasone are demonstrating promising results in other indications but are associated with a high rate of complications4,5 Increased IOP, cataract, retinal detachment, endophthalmitis A 5-year prospective, randomized, controlled, multicenter (15 medical centers) by Fung75,76 suggested that patients with chronic ACME because of vitreous adherence to the wound and pupil distortion (without an intraocular lens implant) who underwent PPV improved compared with the control group. A confounding variable, however, was the use of corticosteroids in the treatment group.( Fung WE, Vitrectomy-ACME Study Group. Vitrectomy for chronic aphakic cystoid macular edema. Results of a national, collaborative, prospective, randomized investigation. Ophthalmology 1985;92:1102– Fung WE. The national, prospective, randomized vitrectomy study for chronic aphakic cystoid macular edema. Progress report and comparison between the control and nonrandomized groups. Surv Ophthalmol 1984;28:569–576. A recent retrospective study77 analyzed 23 eyes with chronic (mean time between cataract surgery and vitrectomy = 32 months) PCME refractory to medical therapy, Nd:YAG vitreolysis, or both with less severity than previously studied by Fung.75,76 Patients with any vitreous incarceration in the wound or vitreal–corneal touch were excluded from this study. Notably, all eyes had resolution of PCME by biomicroscopy after vitrectomy. After a mean follow-up period of / months, the median preoperative BCVA was 20/200 and the median postoperative BCVA was 20/60 (P , ). The postoperative VA improved by a mean of 3.3 Snellen lines, suggesting that PCME can occur in eyes with no clinical vitreous disturbance (Pendergast SD, Margherio RR, Williams GA, Cox MS. Vitrectomy for chronic pseudophakic cystoid macular edema. Am J Ophthalmol 1999;128:317–323.) 1. Schmier JK et al. Retina 2007;27: Loewenstein A & Zur D. Dev Ophthalmol 2010;47: Cho H & Madu A. J Inflamm Res 2009;2:37 4. Jaffe GJ et al. Ophthalmology 2006;113: Williams GA et al. Am J Ophthalmol 2009;147:1048 6. Fung WE et al. Ophthalmology 1985;92: 7. Pendergast SD et al. Am J Ophthalmol 1999;28:

39 Autorizzato dall’EMA per RVO e Uveiti non infettive
Desametasone 5 VOLTE + POTENTE DEL TA ALTA SOLUBILITA’ IN ACQUA IMPIANTO BIODEGRADABILE 700 MICROg EFFETTO TERAPEUTICO : 6 MESI Verificare autorizzazione FDA ed EMA Nell’rvo in assenza di studi testa a testa non possiamo stabilire quale farmaco sia superiore ozurdex vs lucentis. Nella scelta quindi considerare la compliance del pz, glaucoma, precedente vitrectomia Per quanto riguarda l’EMD Ozurdex autorizzato in 648 rimborsabile da ssn nei casi resistenti o allergici al lucentis ( Aifa ) Razionale degli inserti per ridurre ilnm delle iniezioni Autorizzato dall’EMA per RVO e Uveiti non infettive

40 Etiopatogenesi Infiammazione (Sollecitazioni sul segmento anteriore /iride) Attivazione cascata infiammatoria ed up-regulation dei mediatori infiammatori: prostaglandine, leucotrieni, citochine (VEGF, interleuchine) Alterazione della BRB Heping et al. Cataract Surgery Induces Retinal Pro-inflammatory Gene Expression and Protein Secretion. Investigative Ophthalmology & Visual Science, January 2011, Vol. 52 Hyung et al., Etiology and treatment of the inflammatory causes of cystoid macular edema Journal of Inflammation Research 2009:2 37–43

41 Mechanism of action of NSAIDs and corticosteroids2
Trattamento Corticosteroidi e anti-inflammatori non-steroidei (NSAIDs) agiscono sulle PG con differenti meccanismi La somministrazione topica mostra maggiori vantaggi rispetto a quella sistemica ( migliore penetrazione)1 NSAIDS1 (e.g. ketorolac, diclofenac, nepafenac, bromfenac) Some studies show benefit; no apparent difference between products Corticosteroids1 (difluprednate, loteprednol, rimexolone) Topical application first; then periocular or intraocular in persistent cases Leukotrienes Mechanism of action of NSAIDs and corticosteroids2 Corticosteriods and NSAIDs are used because they suppress prostaglandin-induced inflammation (via distinct mechanisms) In response to various stimuli, cell membrane lipids are converted into arachidonic acid by the enzyme phospholipase A2. Further catalyzation by cyclooxygenase (COX) yields prosta- glandin-type mediators (endoperoxides). Corticoste- roids inhibit prostaglandin synthesis by inhibiting the enzyme phospholipase A2. Whereas, aspirin and various NSAIDs (indomethacin, etc) inhibit prosta- glandin synthesis by inhibiting the enzyme COX further along in the pathway.1 Topical application of NSAIDs does provide adequate drug concentration to suppress prostaglandin synthesis in the anterior segment; however, it may not necessarily lead to sufficient concentration in the posterior segment. It is unclear if the drug has to reach the retina or whether the prostaglandins may be synthesized elsewhere (i.e., anterior uvea). As described earlier, NSAIDs reduce prostaglandin levels by the inhibition of cyclooxyge- nase. Of the 2 main isoforms of cyclooxygenase, COX-1 and COX-2, the latter may have an important role in inflammatory disease processes specifically in the retina where COX-2 is the predominant isoform present in human retinal pigment epithelial cells and found to be increased in inflammatory states.34 Because prostaglandins may be important in inducing VEGF,35 Prosta- glandin E2 production is regulated via cyclooxygenase enzymes— cyclooxygenase-1isaubiquitousprotein important to physiologic housekeeping functions, whereas cyclooxygenase-2 is an inducible enzyme primarily responsible for increased prostaglandin pro- duction during inflammation.20 Newer (but expensive) topical NSAIDs such as bromfenac and nepafenac claim enhanced penetration to the posterior segment. However, the research reaching this conclusion was undertaken largely in animals.57–59 recurrences are all too common when corticosteroids wear off. The long-term benefit of corticosteroids is thus uncertain. Lipooxygenase Tromboxane A2 Phospholipids cell membrane Phospholipase A2 Arachidonic acid Cyclooxygenase Prostaglandins (PGE2, PGF2, PGD2) Corticosteroids NSAIDs Prostacyclin PGl2 1. Loewenstein A & Zur D. Dev Ophthalmol 2010;47:148 2. Cervantes-Costes G et al. Clin Ophthalmol 2009;3:219