Classification and quantification of risk factors and treatment strategies for ocular hypertension and primary open-angle glaucoma

Qëndresë, Daka (2015) Classification and quantification of risk factors and treatment strategies for ocular hypertension and primary open-angle glaucoma. PhD thesis, Sveučilište u Zagrebu.

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Abstract

AIM: A systematic synthesis of the existing research evidence in the field of POAG is an appropriate methodological approach to achieve the aim of improved overall management of the disease. In the present study we focused on evidence on risk factors other than intraocular pressure (IOP) that are potentially modifiable and/or could be used for timely identification of people at high risk of POAG; and on relative efficacy, tolerability and cost-effectiveness profile of mono-compound topical IOP-lowering medications in treatment of POAG/OHT. METHODS: Systematic review of systematic reviews/meta-analysis of primary prognostic studies and randomized controlled trials (RCTs). A thorough and sensitive search of Medline, Scopus and Cochrane Databases was performed. Methodological quality of reviews and quality of evidence were assessed using the AMSTAR checklist and the GRADE system, respectively. Comprehensive Meta-Analysis softaware version 2.2.064 2011 ( Biostat Inc., Englewood, NJ, USA) and SAS for Windows 9.2 (SAS Institute Inc., Cary, NC, USA) (macros for multiple modifier meta-regression) were used for data analyses. Conclusions were based on the evaluation of the best available evidence. RESULTS: 3606 records were identified through two different search strategies; 25 studies met the inclusion criteria for evaluation of POAG risk factors and 16 for the evaluation of efficacy and safety of mono-compound topical IOP-lowering drugs. Only six reviews achieved an overall "moderate” quality of evidence. Reviews dealing with risk factors were of low quality in general, whereas individual studies indicated that there were no association between smoking and POAG and a weakly increased risk of POAG in diabetic women. “Moderate quality” reviews dealing with therapy indicate that prostaglandin analogues (PGAs) should be considered equivalent regarding efficacy, but latanoprost is relevantly better tolerated than bimatoprost or latanoprost. Non-PGA compounds do not relevantly differ between each other in either efficacy or safety. Timolol and brimonidine are relevantly less effective than all PGAs. The same is true for CAI vs. bimatoprost. Regarding tolerability, timolol is superior to all PGAs and brimonidine and CAI are superior to bimatoprost. Conclusion: Several potential risk factors for POAG apart from IOP were identified, however, no conclusion regarding their contribution could be drawn as the available information derives from low quality evidence. Available evidence of mono-compound IOP-lowering medications in treatment of POAG/OHT was identified. Moderate quality evidence indicates latanoprost as a mono-compound topical treatment with a most favourable trade-off between benefits and harms.

Abstract in Croatian

CILJ: U svrhu poboljšanja cjelokupnog upravljanja bolešću, poduzeta je sustavna sinteza postojećih znanja u području primarnog glaukoma otvorenog kuta (POAG). U ovom smo se istraživanju usredotočili na dokaze o postojanju čimbenika rizika za POAG, mimo povišenog intraokularnog tlaka (IOP), koji su potencijalno promjenjivi i/ili bi se mogli koristiti za pravovremenu identifikaciju ljudi s visokim rizikom za POAG; i na relativnu djelotvornost, podnošljivost i isplativost monokomponentnih topikalnih lijekova za snižavanje IOP u liječenju POAG, odnosno, okularne hipertenzije (OHT). METODE: Pregled sustavnih pregleda/meta-analiza primarnih prognostičkih studija i randomiziranih kontroliranih pokusa (RCT). Poduzeto je temeljito i osjetljivo pretraživanje Medline, Scopus i Cochrane baze podataka. Metodološka kvaliteta ocijenjena pomoću AMSTAR ljestvice a ukupna kvaliteta dokaza uporabom GRADE sustava. Za analizu podatka korišteni su ComprehensiveMetaAnalysis softaware verzija 2.2.064 2011. (Biostat Inc., New Jersey, USA) i SAS za Windows 9.2 (SAS Inc., Cary, NJ, USA) (makro za multiplu meta-regresiju). Zaključci se temelje na najboljim dostupnim dokazima. REZULTATI: Identificirano je 3606 zapisa uporabom dvije različite strategije pretraživanja; 25 studija zadovoljilo je kriterije za uključivanje u procjenu čimbenika rizika za POAG, a 16 studije za uključivanje u procjenu djelotvornosti i sigurnosti monokomponentnih topikalnih lijekova za snižavanje IOP u bolesnika s POAG/OHT. Samo šest sustavnih pregleda postiglo je "srednju" razinu kvalitete dokaza. Studije čimbenika rizika bile su, sveukupno, niske kvalitete, a pojedinačne studije pokazale su da nema povezanosti između pušenja i POAG, te da je u žena s dijabetesom blago povećan rizik za nastanak POAG. Dokazi " srednje kvalitete" pokazuju da prostaglandinske analoge (PGA) treba smatrati ekvivalentnima u pogledu djelovornosti, te da je latanoprost znatno bolje podnošljiv od travoprosta i bimatoprosta.. Ostali, „ne-PGA“, lijekovi, ne razlikuju se bitno jedni od drugih u pogledu djelotvornosti i sigurnosti. Timolol i brimonidin relevantno su manje djelotvorni od svih PGA. Isto vrijedi i za inhibitore karboanhidraze (CAI) u usporedbi s bimatoprostom. U pogledu podnošljivosti, timolol je superioran u odnosu na sve PGA i brimonidin, a CAI su superiorni bimatoprostu. ZAKLJUČAK: Identificirano je nekoliko potencijalnih čimbenika rizika za POAG osim IOP, međutim, s obzirom na nisku razinu dokaza, nisu mogući racionalni zaključci o doprinosu pojedinih čimbenika riziku za nastanak POAG. Dokazi srednje kvalitete pokazuju da kao monokomponentni topikalni tretman, latanoprost ima najbolji odnos djelotvornosti i sigurnosti.

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