Efficacy and safety of ranibizumab monotherapy versus ranibizumab in combination with verteporfin photodynamic therapy in patients with polypoidal choroidal vasculopathy: 12-month outcomes in the Japanese cohort of EVEREST II study

Figures & data

Figure 1 Study design and treatment schedule.

Notes: Included Japanese patients. *Ranibizumab was administered PRN as per protocol-specific retreatment criteria if there was a BCVA loss or presence of disease activity as seen in OCT. ^#vPDT/sham PDT^‡ was administered PRN as per protocol-specific retreatment criteria based on presence of active polyp(s) on ICGA with a minimum interval between two PDT treatments of at least 3 months. The interval between two ranibizumab treatments was at least 28 days.
Abbreviations: BCVA, best-corrected visual acuity; D, Day; ICGA, indocyanine green angiography; OCT, optical coherence tomography; PRN, pro re nata; vPDT, verteporfin photodynamic therapy.

Table 1 Patient demographics, baseline disease, and ocular characteristics (randomized set)

Characteristics	Japanese cohort
	Ranibizumab 0.5 mg + vPDT (n=46)	Ranibizumab 0.5 mg (n=38)
Age, mean (SD), years	72.9 (7.4)	72.9 (7.5)
Gender, male, n (%)	38 (82.6)	28 (73.7)
BCVA, mean (SD), letters	64.3 (11.3)	61.6 (11.6)
BCVA category, n (%)
<39	1 (2.2)	1 (2.6)
39 to <54	8 (17.4)	8 (21.1)
54 to <74	25 (54.3)	21 (55.3)
≥74	12 (26.1)	7 (18.4)
Type of lesion, n (%)
100% classic	0 (0.0)	0 (0.0)
Predominantly classic	1 (2.2)	0 (0.0)
Minimally classic	0 (0.0)	7 (18.4)
Occult with no classic component	39 (84.8)	26 (68.4)
Cannot grade	6 (13.0)	5 (13.2)
CSFT, mean (SD), µm	404.1 (128.3)	411.3 (149.7)
CCT, mean (SD), µm	313.3 (95.8)	258.2 (77.0)
Presence of SRF, n (%)	43 (93.5)	37 (97.4)
Presence of IRF, n (%)	27 (58.7)	24 (63.2)
Presence of visible cysts, n (%)	14 (30.4)	15 (39.5)
Presence of polyp, n (%)	46 (100.0)	38 (100.0)
Polyp size, mean (SD), mm^2	0.318 (0.3)	0.346 (0.4)
BVN size, mean (SD), mm^2	2.045 (1.8)	2.224 (1.6)
GLD (polyp + BVN), mean (SD), µm	2,193.5 (945.6)	2,362.6 (827.3)

Notes: Randomized set consisted of all randomized participants. Percentages are based on the total number of participants in the randomized set in the respective treatment arms.

Abbreviations: BCVA, best-corrected visual acuity; BVN, branching vascular network; CCT, central choroidal thickness; CSFT, central subfield thickness; GLD, greatest linear dimension; IRF, intraretinal fluid; SRF, subretinal fluid; vPDT, verteporfin photodynamic therapy.

Figure 2 Randomization and patient disposition in the Japanese cohort.

Notes: *Of the 322 patients who were randomized 1:1 in the EVEREST II study, 84 patients identified themselves as belonging to the Japanese ethnicity. Percentages are based on the total number of patients in the randomized set in the respective treatment arm.
Abbreviation: vPDT, verteporfin photodynamic therapy.

Figure 3 Assessment of BCVA outcomes over the 12-month study period.

Notes: (A) Mean BCVA and mean change at baseline and Month 12 (FAS; LOCF). (B) Proportion of patients with BCVA ≥69 letters at baseline and Month 12 (FAS). The FAS comprised all participants who were assigned to a treatment regimen. The total counts presented are the counts of patients in the specific treatment arm who attended the specific visit. These total counts are used as the denominator for the percentages.
Abbreviations: BCVA, best-corrected visual acuity; FAS, full analysis set; vPDT, verteporfin photodynamic therapy; LOCF, last observation carried forward; n, number of patients.

Figure 4 Proportion of participants with complete polyp regression by study visits up to Month 12 (FAS).

Notes: Values assessed by the Central Reading Center using ICGA. The FAS comprised all participants who were assigned to a treatment regimen. Number values indicate the total number of participants in the FAS in the respective treatment arm. Percentages are computed by considering the total number of participants in the respective treatment arm who attended the specific visit as a denominator.
Abbreviations: FAS, full analysis set; ICGA, indocyanine green angiography; vPDT, verteporfin photodynamic therapy.

Figure 5 Mean change in CSFT and CCT, and proportion of participants with disease activity.

Notes: (A) Mean CSFT change from baseline to Month 12 (FAS). (B) Mean reduction in CCT from baseline to Month 12 (FAS). (C) Proportion of participants with disease activity by visit (FAS). The FAS comprised all participants who were assigned to the treatment regimen. Number values indicate the total number of participants in the FAS in the respective treatment arm. Percentages are computed by considering the total number of participants in the respective treatment arm who attended the specific visit as a denominator.
Abbreviations: CSFT, central subfield thickness; CCT, central choroidal thickness; FAS, full analysis set; M, month; vPDT, verteporfin photodynamic therapy.

Table 2 Number of ranibizumab injections and vPDT/sham PDT treatments administered prior to month 12 in the Japanese cohort (safety set)

Characteristics	Ranibizumab 0.5 mg + vPDT (n=46)a	Ranibizumab 0.5 mg (n=38)a
Number of ranibizumab injections
Mean (SD)	4.2 (1.65)	7.3 (3.26)
Median (IQR)	4.0 (3.0, 5.0)	7.0 (4.0, 11.0)
Number of vPDT/sham PDT
Mean (SD)	1.2 (0.43)	2.4 (1.13)
Median (IQR)	1.0 (1.0, 1.0)	2.0 (2.0, 4.0)

Notes:

a Safety set consisted of all patients who received at least one application of study treatment and had at least one post baseline safety assessment. n is the total number of subjects with at least one injection.

Abbreviations: IQR, interquartile range; vPDT, verteporfin photodynamic therapy.

Table 3 Ocular AEs regardless of study drug relation ship up to month 12 (safety set)

Preferred term, n (%)	Ranibizumab 0.5 mg + vPDT (n=46)	Ranibizumab 0.5 mg (n=38)
Ocular AEs, total	11 (23.9)	6 (15.8)
Asthenopia	2 (4.3)	0 (0.0)
Blepharospasm	1 (2.2)	0 (0.0)
Cataract	0 (0.0)	2 (5.3)
Conjunctivitis allergic	0 (0.0)	1 (2.6)
Conjunctival deposit	1 (2.2)	0 (0.0)
Conjunctival hemorrhage	1 (2.2)	0 (0.0)
Corneal disorder	0 (0.0)	1 (2.6)
Eye hemorrhage	1 (2.2)	0 (0.0)
Eyelid edema	0 (0.0)	1 (2.6)
Eye pain	1 (2.2)	0 (0.0)
Hyphema	1 (2.2)	0 (0.0)
Corneal injury	1 (2.2)	0 (0.0)
Increased IOP	1 (2.2)	0 (0.0)
Retinal hemorrhage	1 (2.2)	0 (0.0)
Subretinal fluid	1 (2.2)	0 (0.0)
Blurred vision	1 (2.2)	0 (0.0)
Visual field defect	1 (2.2)	0 (0.0)
Vitreous floaters	1 (2.2)	1 (2.6)

Note: The safety set consisted of all patients who received at least one application of study treatment and had at least one post baseline safety assessment.

Abbreviations: AEs, adverse events; IOP, intraocular pressure; vPDT, verteporfin photodynamic therapy.