Clinical utility and differential effects of prostaglandin analogs in the management of raised intraocular pressure and ocular hypertension

Figures & data

Table 1 Summary of meta-analyses of randomized control trials of prostaglandin analog use as monotherapy in ocular hypertension and open-angle glaucoma

Author/year/sponsor	PGA randomized	No. of trials	N	Cross-over studies	Single-blind studies	Quality scores	Duration (months)	%Without OAG or OH	Summary of IOP-lowering efficacy
Cheng^Citation89/2008/Nil	Lat, Bim	13	1302	Yes	Yes	Jadad	1–6	17.0a	WMD %IOPR: Bim vs Lat = 5.60%, P <0.001 in favor of Bim
Zhang^Citation115/2001/Nil	Lat, Tim	11	1256	Yes	Yes	Jadad	1–12	10.9	%IOPR: Lat 30.2% >Tim 26.9%. %IOP-lowering difference = 5% (1.6 mmHg), P <0.001
Fung^Citation146/2007/Nil	Lat, Brim	14	1784	Yes	Yes	No	1–12	3.4	WMD %IOPR: Lat vs Tim = 1.10 mmHg, CI 0.57–1.63, P = 0.001 in favor of Lat
Einarson^Citation145/2000/Pharmacia	Lat, Brim	9	1168	NR	No	Jadad	Up to 6	NR	IOPR: Lat 8.0 mmHg > Brim 6.2 mmHg, P =0.045
Aptel^Citation88/2008/Nil	Lat, Bim, Trav	8	1610	No	No	Jadad	1–6	0	IOPR: Bim > Trav (at 0800 and 1200 h) >Lat (all time points)
Eyawo^Citation90/2008/Pfizer	Lat, Bim, Trav	16	2664(IR)	No	Yes	No	3–12	8.7	WMD %IOPR: Trav vs Lat = −0.24 mmHg, CI −0.87–0.38, P = 0.45, Trav vs Bim = 0.88 mmHg, CI 0.13–1.63, P = 0.02, Lat vs Bim = 0.73 mmHg, CI 0.10–1.37, P = 0.02. Authors state similar efficacy effects
Denis^Citation91/2007/Alcon	Lat, Bim, Trav	9	1318	No	Yes	No	0.5–12	0.9	Difference %IOPR: Trav vs Lat = −0.98 mmHg, CI −2.08–0.13, P = 0.08. Bim vs Lat = −1.04 mmHg, CI −2.11; 0.04, P = 0.06. Pooled Trav or Bim vs Lat = −1.0 mmHg, CI −1.91, −0.10, P = 0.03 in favor of pooled Trav or Bim
Holmstrom^Citation128/2005/Allergan	Lat, Bim, Trav, Tim	42	9295	Yes	Yes	No	0–6	NR	WM %IOPR: Bim 30.3% > Trav 28.7% > Lat 26.7% > Tim 22.2%
Li^Citation105/2006/Nil	Lat, Bim, Trav, Tim	12	3048	NR	Yes	No	0.5–12	3.8	WMD %IOPR: Trav vs Tim = −0.81 mmHg, P = 0.00001 in favor of Trav, Trav vs Bim = 0.08 mmHg, P = 0.8. Trav vs Lat = −0.57 mmHg, P =0.07 in favor of Trav
Hodge^Citation158/2008/Nil	Lat, Brim, Dorz	8	1722	Yes	NR	Jadad	3–6	5.8	WMD in IOPR: Lat vs Brim = −1.04 mmHg, P = 0.30. Lat vs Dorz = −2.64 mmHg, P < 0.00001 in favor of Lat
Cheng^Citation186/2009/Nil	Lat, Dorz + Tim	14	2149	Yes	Yes	Jadad	1–12	14.3 (IR)	WMD %IOPR: Subjects uncontrolled on timolol treatment: Lat vs Dorz/Tim = 3.12%, CI 0.47– 5.78, Significant. Subjects not on baseline timolol treatment: Lat is as effective as Dorz/Tim
Stewart^Citation162/2008/Nil	Lat, Bim, Trav, Tim, Brim, Dorz	11	386	Yes	Yes	Delphi	1–2	NR	24-Hour %IOPR: Bim 29% > Trav 27% > Lat 24%, >Tim 19% > Dorz 19% > Brim 14%
van der Valk^Citation84/2005/Nil	Lat, Bim, Trav, Btx, Tim, Dorz, Brinz, Brim	28	6953(trough) 6841(peak)	NR	Yes	Delphi	1–6	2.8 (IR)	%IOPR: At peak: Bim 33% > Lat 31% = Trav 31% > Tim 27% > Brim 25% > Btx 23% > Dorz 22% >Brinz 17% At trough: Trav 29% > Bim 28% = Lat 28% > Tim 26% > Btx 20% > Brim 18% > Brinz 17% = Dorz 17%

Abbreviations: Bim, bimatoprost 0.03%; Brim, brimonidine 0.2%; Brinz, brinzolamide 1.0%; Btx, betaxolol 0.5%; CI, 95% confidence intervals; IOP, intraocular pressure; IOPR, intraocular pressure reduction; IR, incompletely reported; Lat, latanoprost 0.005%; NR, not reported; OH, ocular hypertension; OAG, open-angle glaucoma; Trav, travoprost 0.004%; WM. weighted mean; WMD, weighted mean difference; Tim, timolol.

a Excludes NTG subjects.

Table 2 Selected multi-center, randomized control trials of greater than 1-month duration comparing efficacy of prostaglandin analogs in ocular hypertension and open-angle glaucoma

First author/year/sponsor	Design	Randomized PGA	Duration (months)	N	Mean age (yrs)/%female/% withdrawal	No. of OAG/OH/Othera	Results summary
Parrish^Citation85/2003/Pharmacia	SB-P	Lat vs Bim vs Trav	3	410	65/58.0/4.4	309/95/6	Mean ± SEM IOP reduction from baseline was equivalent among treatment groups: Lat 8.6 ± 0.3 mmHg, Bim 8.7 ± 0.3 mmHg, Trav 8.0 ± 0.3 mmHg, P = 0.128. Mean IOP level was similar across treatment groups at 12 weeks
DuBiner^Citation63/2001/Allergan	DB-P	Lat vs Bim	1	43	66.5/51.1/7.0	19/24/0	Greater non-significant mean IOP reduction (average of 4 diurnal readings) from baseline with Bim (6.96 mmHg) than Lat (5.48 mmHg), P = 0.0572, and IOP ≤15 mmHg (Bim 31.6% vs Lat 19.0%)
Gandolfi^Citation64/2001/nil disclosed	SB-P	Lat vs Bim	3	232	61.7/62.5/7.8	132/81/19	Greater significant mean IOP reduction from baseline with Bim at 1200 and 1600 h, but not at 0800 and 2000 has Lat. IOP ≤13 mmHg more frequent in Bim group (P ≤ 0.006)
Noecker^Citation86/2003/Allergan	SB-P	Lat vs Bim	6	269	61.3/61.7/7.4	150/93/26	Mean difference in IOP reduction significantly favored Bim compared with Lat: 1.5 mmHg at 0800 (P < 0.001), 2.2 mmHg at 1200 (P <0.001), and 1.2 mmHg at 1600 (P = 0.004). Diurnal IOP was lower with Bim (16.5 to 17.4 mmHg) than Lat (17.6 to 18.9 mmHg), P ≤ 0.008. IOP ≤13 mmHg was achieved significantly more in Bim group
Walters^Citation78/2004/Allergan	SB-P	Lat vs Bim	1	76	58.8/61.8/3.9	48/28/0	Mean IOP reduction and %IOP reduction from baseline was greater with Bim (9.3 mmHg, 40.3%) than Lat (7.4 mmHg, 33.3%) but not significant. Target IOP ≤15 mmHg achieved more often in Bim- than Lat-treated eyes, P ≤ 0.038
Netland^Citation68/2001/Alcon	SB-P	Lat vs Trav	3	390	64.2/51.5/5.3	259/126/5	Mean IOP reduction from baseline was similar for Trav (6.6 to 8.1 mmHg) and Lat (6.2 to 8.1mmHg). Mean IOP at all treatment visits for Trav was 17.5 to 19.7 mmHg and for Lat, 17.9 to 19.5 mmHg. Mean IOP was 0.8 mmHg lower for Trav than Lat, P =0.0191. Target IOP reduction of ≥30% or final IOP≤17 mmHg was achieved with Trav (54.7%) more than Lat (49.6%), P =0.0430
Cantor^Citation87/2006/Allergan	SB-P	Bim vs Trav	6	157	65.0/60.5/10.8	108/48/1	Mean IOP reduction and %IOP reduction from baseline was significantly favorable for Bim (7.1 mmHg, 27.9%) than Trav (5.7 mmHg, 23.3%) at 0900, P = 0.014, but not-significantly favorable at 1300 and 1600. Significantly more Bim- (64.5%) treated subjects achieved IOP reduction ≥25% than Trav- (39.5%) treated, P = 0.002

Abbreviations: Bim, bimatoprost 0.03%; DB-P, double-blind; parallel group; IOP, intraocular pressure; Lat, latanoprost 0.005%; NR, not reported; OH, ocular hypertension; PGA, prostaglandin analog; OAG, open-angle glaucoma; SB-P, single-blind; parallel group; Trav, travoprost 0.004%.

a Includes pseudo-exfoliative, pigment dispersion, and angle-closure glaucoma.

Table 3 Characteristics of double-blind randomized control trials of 1 to 9 months’ duration comparing prostaglandin analogs with timolol 0.5% twice daily for ocular hypertension and open-angle glaucoma

Author/year/location	Design	Randomized PGA	Duration (months)	N	Mean age (yrs)/%female/% withdrawal	No. of OAG/OH/Othera	% diurnal IOP reduction from baseline		P-value
							PGA	Timolol
Alm^Citation71/1995/Scandb	DB-P DB-C	Lat mane or nocte	6	267	67/56.6/6	91/123/53	35 (nocte) 31 (mane)	27	P =0.001
Camras^Citation73/1996/USAb	DB-P	Lat nocte	6	268	62/57.5/7	84/170/14	27	20	P =0.001
Watson^Citation72/1996/UKb	DB-P	Lat nocte	6	294	65/35.0/9	121/148/25	33.7	32.7	NS
Mishima^Citation81/1996/Japan	DB-P	Lat mane	3	178	57/51.1/11	NR	26.8	19.9	P < 0.001
Brandt^Citation124/2001/USAb	DB-P	Bim nocte or bd	3	596	62/56.0/7.4	373/218/5	35.2 (nocte) 30.4 (bd)	26.2	P < 0.001
Whitcup^Citation125/2003/USAb	DB-P	Bim nocte or bd	3	602	61/53.7/8.6	300/284/18	32.4 (nocte) 25.2 (bd)	22.7	P < 0.001
Goldberg^Citation121/2001/Variousb	DB-P	Trav nocte	9	382	63/49.7/3.1	208/147/27	30.8–31.6	25.1–27.9	P ≤ 0.0001
Fellman^Citation122/2002/USAb	DB-P	Trav nocte	6	396	NR/52.5/2.8	251/132/13	From pooled visits, Trav was superior to Tim		P < 0.0130

Abbreviations: bd, twice daily; Bim, bimatoprost 0.03%; DB-C, double-blind, cross-over; DB-P, double-blind, parallel; Lat, latanoprost 0.005%; mane, every morning; nocte, every night; NR, not recorded; NS, not significant; OH, ocular hypertension; OAG, open-angle glaucoma; PGA, prostaglandin analog; Scand, Scandinavia; Trav, travoprost 0.004%; wks, weeks; Tim, timolol.

a Includes pseudoexfoliative, pigment dispersion and other secondary glaucomas;

b indicates sponsorship by Pharmacia Inc.

Table 4 Differential adverse event rates among prostaglandin analogs as reported in multi-center, randomized control trials summarized in Table 2

First author/year	N	Reported rates of adverse events
		Ocular	Systemic
Parrish^Citation85/2003	410	CH: Bim 68.6%, Trav 58.0%, Lat 47.1%, P = 0.001 Bim vs Lat Moderate CH: Bim 15.3%, Trav 10.1%, Lat 5.9% Eye irritation: Bim 10.9%, Trav 4.3%, Lat 6.6% Eyelash growth: Bim 2.9%, Trav 0.7%, Lat 0% Skin discoloration: Bim 2.9%, Trav 2.9%, Lat 1.5%	Bim 18.2%, Trav 16.7%, Lat 16.9%. Events reported >2% were nasopharyngitis, upper respiratory tract infection, headache
DuBiner^Citation63/2001	43	CH: Bim 14.3%, Lat 14.3%
Gandolfi^Citation64/2001	232	CH: Bim 36.1%, Lat 14.2%, P ≤ 0.001. Mild Eyelash growth: Bim 12.6%, Lat 4.4%, P =0.026 Ant uveitis: 1 subject each No CME or iris change	Headache: 4.4% Lat vs 0% Bim, P = 0.026
Noecker^Citation86/2003	269	CH (slit-lamp): Bim 55.4%, Lat 42.5%, P <0.001 Eyelash growth: Bim > Lat, P = 0.064 Iris change: 1 subject Bim Ant uveitis: 1 subject Lat No CME	12 serious adverse events. None reported to be related to study medication
Walters^Citation78/2004	76	CH: Bim 39.5%, Lat 15.8%, P =0.021. Mild 14/15 cases Eye pruritis: Bim 13.2%, Lat 2.6%, P =0.20 Ant uveitis: 1 subject Lat No CME	–
Netland^Citation68/2001	390	CH: Trav 38.0%, Lat 27.6%, mainly mild Eyelash growth: Trav 57.1%, Lat 25.8% Iris change: Trav 3.1%, lat 5.2% No anterior uveitis, No CME	–
Cantor^Citation87/2006	157	CH: Bim 21.1%, Trav 14.8%, P =0.326 Ocular itching: Bim 2.3%, Trav 7.4%, P = 0.278 Iris change: 1 subject Bim	–

Abbreviations: Ant, anterior; Bim, bimatoprost 0.03%; CH, conjunctival hyperemia; CME, cystoid macular edema; Lat, latanoprost 0.005%; Trav, travoprost 0.004%.

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