Combination verteporfin photodynamic therapy ranibizumab-dexamethasone in choroidal neovascularization due to age-related macular degeneration: results of a phase II randomized trial

Figures & data

Figure 1 Results of a phase II randomized trial retreatment criteria.

Abbreviations: CNV, choroidal neovascularization; FA, fluorescein angiography; OCT, optical coherence tomography; PDT, photodynamic therapy.

Figure 2 Subject disposition through 24 months.

Figure 3 Cumulative mean number of visits at which retreatment was applied (excluding day 0).

Abbreviation: ITT, intent to treat.

Table 1 Summary of treatmenta

	Month 12				Month 24
	Quarter-fluence triple (N=39)	Half-fluence triple (N=39)	Half-fluence double (N=43)	Ranibizumab (N=41)	Quarter-fluence triple (N=39)	Half-fluence triple (N=39)	Half-fluence double (N=43)	Ranibizumab (N=41)
Number of treatment visitsb	4.97	4.22	5.13	6.74	6.92	5.34	6.92	9.68
95% CI	3.96–5.98	3.37–5.08	4.16–6.10	5.65–7.82	5.35–8.49	4.09–6.60	5.46–8.38	7.74–11.62
P-valuec	0.02	<0.001	0.03	–	0.03	<0.001	0.02	–
Number of proceduresb	12.62	10.75	8.97	6.74	17.55	14.00	12.16	9.68
95% CI	10.36–14.87	8.94–12.56	7.48–10.47	5.65–7.82	14.00–21.11	11.09–16.91	9.88–14.45	7.74–11.62
P-valueb	<0.001	<0.001	0.02	–	<0.001	0.01	0.10	–
Number of retreatment visits (excludes day 0)	3.97	3.22	4.13	5.74	5.92	4.34	5.92	8.68
95% CI	2.96–4.98	2.37–4.08	3.16–5.10	4.65–6.82	4.35–7.49	3.09–5.60	4.46–7.38	6.74–10.62
P-valuec	0.02	<0.001	0.03	–	0.03	<0.001	0.02	–
Number of procedures (excludes day 0)	9.62	7.75	6.97	5.74	14.55	11.00	10.16	8.68
95% CI	7.36–11.87	5.94–9.56	5.48–8.47	4.65–6.82	11.00–18.11	8.09–13.91	7.88–12.45	6.74–10.62
P-valueb	0.003	0.06	0.18	–	0.01	0.18	0.33	–
Number of retreatment visits (excludes all mandatoryd)	3.97	3.22	4.13	3.79	5.92	4.34	5.92	6.81
95% CI	2.96–4.98	2.37–4.08	3.16–5.10	2.72–4.87	4.36–7.49	3.09–5.60	4.46–7.38	4.89–8.72
P-valueb	0.80	0.40	0.64	–	0.46	0.33	0.45	–
Number of procedures (excludes all mandatoryd)	9.62	7.75	6.97	3.79	14.55	11.00	10.16	6.81
95% CI	7.36–11.87	5.94–9.56	5.48–8.47	2.72–4.87	11.00–18.11	8.09–13.91	7.88–12.48	4.89–8.72
P-valueb	<0.001	<0.001	<0.001	–	<0.001	0.02	0.03	–

Notes: In the combination therapy groups, a ranibizumab injection alone resulted in the visit being considered a treatment/retreatment visit.

a The primary variable is highlighted. All other analyses were exploratory.

b All treatments (including day 0) through month 12.

c Compared with RM.

d Excludes day 0 treatment in all groups and months 1 and 2 treatments in the RM group.

Abbreviations: CI, confidence interval; RM, ranibizumab monotherapy.

Figure 4 Mean visual acuity letter score change from baseline through 12 months (1 line equals 5 letters; ITT LOCF).

Abbreviations: ITT, intent to treat; LOCF, last observation carried forward.

Table 2 Summary of AE

AE category	Number of subjects (%)
	Quarter-fluence triple (N=39)	Half-fluence triple (N=39)	Half-fluence double (N=43)	Ranibizumab (N=41)
All AE	38 (97)	36 (92)	37 (86)	40 (98)
All ocular AE	26 (67)	25 (64)	26 (61)	25 (61)
SAE (not treatment associated)	10 (26)	13 (33)	15 (35)	19 (46)
Deaths	0	3 (8)	2 (5)	5 (12)
Withdrawal due to SAE	0	1 (3)a	0	0
Treatment-associated AEb	19 (49)	17 (44)	20 (47)	11 (27)
Infusion-related back pain	1 (3)	2 (5)	4 (9)	0
Intravenous injection site
Extravasation	1 (3)	1 (3)	3 (7)	0
Pain	1 (3)	1 (3)	3 (7)	0
Photosensitivity reaction	1 (3)c	0	1 (2)d	0
Ocular AE	15 (38)	14 (36)	13 (30)	11 (27)
Choroidal hypoperfusion	0	0	2 (5)e	0
Conjunctivitis	0	2 (5)	1 (2)	1 (2)
Corneal lesion	0	2 (5)	0	0
Eye pain	5 (13)	7 (18)	7 (16)	8 (20)
Increased IOPf	1 (3)	4 (10)	3 (7)	0
Vision abnormal	4 (10)	1 (3)	2 (5)	0
Vision decreased	3 (8)	3 (8)	2 (5)	0
Visual field defect	4 (10)	0	2 (5)	2 (5)
Withdrawal due to treatment-associated AE	0	1 (3)g	0	0
Treatment-associated SAE	2 (5)	2 (5)	1 (2)	0
Increased IOP	0	1 (3)	0	0
Retinal detachment	0	0	1 (2)	0
Retinal tear	1 (3)	0	0	0
Vision decreased	0	1 (3)	1 (2)	0
Visual field defect	0	0	1 (2)	0
Vitreous hemorrhage	1 (3)	0	1 (2)	0
Withdrawal due to SAE	0	1 (3)	0	0
Deaths	0	0	0	0

Notes:

a Due to anxiety.

b As assessed by the Investigator. Difference is statistically significant (P=0.045) between the quarter-fluence triple group (49%) and ranibizumab monotherapy group (27%).

c Reported 2 days after the subject’s second treatment.

d Reported on the day of initial treatment.

e Moderate in intensity and associated with verteporfin photodynamic therapy; not associated with visual symptoms and not serious.

f Defined as an increase of ≥10 mmHg from the previous visit or measurement of ≥25 mmHg. IOP elevations were considered mild except in one subject. Of the seven subjects with treatment-associated increased IOP, two received treatment (paracentesis and topical eye drops).

g Due to the SAE of increased IOP.

Abbreviations: AE, adverse events; IOP, intraocular pressure; SAE, serious adverse events.