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Il controllo circadiano della pressione intraoculare: implicazioni farmacologiche

Il controllo circadiano della pressione intraoculare: implicazioni farmacologiche. N. ORZALESI, P. FOGAGNOLO Università degli Studi di Milano Ospedale San Paolo - Milano. Congresso Nazionale di Farmacologia Oculare Catania, 3 ottobre 2006. IOP represents the main risk factor

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Il controllo circadiano della pressione intraoculare: implicazioni farmacologiche

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  1. Il controllo circadiano della pressione intraoculare: implicazioni farmacologiche N. ORZALESI, P. FOGAGNOLO Università degli Studi di Milano Ospedale San Paolo - Milano Congresso Nazionale di Farmacologia Oculare Catania, 3 ottobre 2006

  2. IOP represents the • main risk factor • for glaucoma. • High IOP is linked to the progression of the disease. • The association between IOP increase and morphological and functional damage is confirmed by experimental glaucoma (photocoagulation or steroid induced, etc.).

  3. Bengtsson B, Heijl A.Diurnal IOP fluctuation: not an independent risk factor for glaucomatous visual field loss in high-risk ocular hypertension. Graefes Arch Clin Exp Ophthalmol. 2005 Jun;243(6):513-8. When separating effects of mean IOP level and mean IOP fluctuation using Cox multiple regression analysis, only IOP level came out as significant (95% CI 1.09-1.38), and IOP fluctuations did not contribute to the risk (95% CI 0.80-1.60). IOP fluctuation depended linearly on IOP level (p<0.0001), i.e. IOP fluctuation was larger in eyes with higher IOP levels. CONCLUSION: IOP fluctuations were not an independent risk factor for the incidence of glaucomatous visual field loss in subjects with ocular hypertension.

  4. IOP From Ritch et al “The Glaucomas, 1996” Day-type curve ? Night-type curve 15 21 3 12

  5. Liu JH. Circadian rhythm of intraocular pressure. J Glaucoma. 1998 Apr;7(2):141-7. • Nocturnal IOP elevation in rabbits IOVS 2006;47:4050-52. • The presence of Cry1 and Cry2 clock genes is essential for the generation of circadian rhythm of IOP in mice.

  6. In the clinical practice: • IOP is measured only during office hours, though… • …a difference of few mmHg within treatments is deemed as clinically significant (EMGTS) • …similar differences during nighttime are ignored hsp

  7. During the night (…glaucoma does not sleep!!!): • Possibility of increased IOP in young adults and in the aging population (Liu, IOVS 1998, IOVS 1999) • Possibility of arterial hypotension (Graham,Ophthalmology 1995) • Significantly greater BP drops in NTG (dippers) (Meyer, BJO 1996) • Different response to hypotensive drugs • nondippers:  BP < 5% overnight • dippers:  BP 5-10% • overdippers:  BP > 10% overnight (Choi et al, IOVS 2006)

  8. Position Tonometer (self?!) Sleep (frequency of measurements) Pathology(healthy/glaucoma) Setting (clinical/lab/home) Age (young/old) CCT, R, L eye 24-hour tonometry: a problem

  9. Remember Sampaolesi! • 148 untreated Jap POAG • IOP < 21 mmHg, office hours (Jap ) • Peaks at night • 20% > 21 mmHg at night • Less nocturnal peaks when sitting • Hara T. et al. Increase of peak IOP during sleep in reproduced diurnal changes by posture. Arch Ophthalmol. 2006;124:165-168.

  10. Measuring IOP every 30-60 minutes for 24 hours, all NTG cases have peaks > 21 mmHg… NTG = POAG !!! Sampaolesi

  11. IOP assessment at 3am, 6am, 9am, 12am 3pm, 6pm, 9pm, 12pm Orzalesi et al, IOVS 2000 1. Tonopen supine position 2. Blood pressure 3. Tonopen sitting position Patient hospitalized Sleep 11 pm-7 am 10 mt distance walking 4. Goldmann applanation tonometry hsp

  12. M i d n i g h t 8 9 P M 6 3 A M 4 2 0 6 A M 6 P M Least-square cos fitting technique Supine (night) Sitting (day) 3 P M 9 A M Healthy young N o o n hsp Healthy aged

  13. Midnight POAG/OHT 8 Healthy aged 9 P M 6 3 A M Orzalesi et al, IOVS 2000 4 2 0 6 A M 6 P M 3 P M 9 A M hsp N o o n LIU et al, IOVS 2003

  14. PARRISH (2003). Latanoprost > bimatoprost (n.s.) • KONSTAS AG. (2005). Latanoprost < Bimatoprost (0.7 mmHg) • NOECKER RS (2003). Latanoprost < Bimatoprost (1.5 mmHg) • DUBINER (2001). Latanoprost < Bimatoprost (decrease of 4.5-8 vs 6-9 mmHg) • EMGTS (2002). 1 mmHg less = 10% progression less

  15. n=30 Latanoprost x 1 Timolol 0.5% x 2 Max difference: 2.3 mmHg (ns) Fogagnolo P, Rossetti L, Mazzolani F, Orzalesi N. Circadian variations in CCT and IOP in patients with glaucoma. Br J Ophthalmol. 2006 Jan;90(1):24-8. hsp

  16. Fluctuations > 5 mmHg in 60% Fogagnolo P, Rossetti L, Mazzolani F, Orzalesi N. Circadian variations in CCT and IOP in patients with glaucoma. Br J Ophthalmol. 2006 Jan;90(1):24-8. hsp

  17. P-value from test of superiority NOT INFERIOR

  18. Konstas et al, Ophthalmology 2006 A well-functioning trabeculectomy provides a statistically lower mean, peak, and range of IOP for the 24-hour day than maximum tolerated medical therapy in advanced glaucoma patients(P < 0,0001) hsp

  19. IOVS 2006;47:2917-2923

  20. Conclusions • Glaucoma is a “24-hour” disease • Nocturnal IOP measurement difficult but needed in special cases • Supine/sitting positions • Progression with good office-hour IOP • NTG • Arterial hypotension, dippers (holter) • Associated clinical signs • Adequate medical/surgical management

  21. Università degli Studi di Milano Dipartimento di Medicina, Chirurgia e Odontoiatria Clinica Oculistica, Ospedale San Paolo

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