• Treatment
• Visudyne ®
• Therapy at a glance
• CNV
• Therapy - a selective approach
• Clinical Development
• Efficacy
• Safety
• Pharmacokinetics
• Pharmacodynamics
• Administration
• Patient Information
• References

Efficacy

Age-related macular degeneration
Predominantly classic CNV in the TAP Investigation
Occult with no classic CNV in the VIP Trial
Minimally classic CNV
Efficacy in Japanese population – Japanese AMD Trial (JAT)
Pathologic myopia
Visual function
Chance of stabilized vision
Visual acuity
Contrast sensitivity
Angiographic outcomes
The ocular histoplasmosis syndrome
Visual function

The efficacy of Visudyne^® therapy has been proven in over 1000 patients in the phase III TAP Investigation and phase IIIb VIP Trial. Working within recommended treatment protocols, the benefits of Visudyne^® therapy were evident as early as 3 months after initial treatment and were sustained throughout the 1- to 2-year follow-up periods. Long-term efficacy data over 5 and 3 years, respectively are being analyzed from the extensions of the TAP Investigation and the pathologic myopia arm of the VIP Trial. Importantly, the efficacy of Visudyne^® therapy has not been compromised by safety concerns.

This chapter reviews the efficacy results relating to the patient groups for whom Visudyne^® therapy is currently indicated, as well as providing topline data from the VIM Trial and the VALIO Study.

Visudyne^® therapy is currently indicated for predominantly classic CNV due to AMD in over 70 countries and for occult with no classic CNV due to AMD in over 35 countries (including the European Union).

Baseline lesion composition has emerged as an important factor for selecting patients with AMD who will benefit from Visudyne^® therapy. Results from the first 12 months of the TAP Investigation showed that while Visudyne^® therapy improved the visual and angiographic outcomes in the overall population compared with placebo, it was most effective in the population with predominantly classic lesions at baseline (n = 242; Visudyne^® 159, placebo 83) (Figure 5.1).⁶⁶ Results at 24 months confirmed the marked treatment benefit in these patients.⁶⁷

Subsequently, data from the AMD arm of the VIP Trial showed that patients with occult with no classic CNV also benefited from Visudyne^® therapy, with the effect being most pronounced in those patients with either smaller lesions (≤4 MPS DA) or lower levels of visual acuity (Snellen equivalent worse than 20/50).⁶⁸

Figure 5.1 A comparison of the percentage of eyes with a visual acuity loss of less than 3 lines at (a) the month 12 and (b) the month 24 examination in the predominantly classic population and the total study population in the phase III TAP Investigation.

Exploratory analyses from the TAP Investigation and the AMD arm of the VIP Trial have shown that baseline lesion size may be an important predictor of treatment benefit with Visudyne^® therapy in patients with occult with no classic CNV or minimally classic CNV.⁸³ In these patients, treatment of smaller lesions was more likely to result in better visual acuity outcomes. However, baseline lesion size did not affect treatment outcomes in patients with predominantly classic CNV where treatment benefits were independent of the size of the lesion. Further prospective trials are required to confirm these findings.

Chance of stabilized vision
Visudyne^® therapy, applied according to a pre-specified treatment protocol, significantly increased the likelihood of stabilizing vision (visual acuity loss of less than 3 lines) in patients with predominantly classic subfoveal CNV secondary to AMD after 12 months of follow-up in the TAP Investigation. This benefit was sustained through 24 months and was recognized as the most clinically relevant endpoint in the trial because the 3-line loss represented a doubling of the visual angle. Visudyne^®-treated patients were more likely to retain vision, compared with placebo, with an absolute difference of 28% between treatment groups at both 12 and 24 months (p <0.001) (Figure 5.2).^66,67 After 24 months of follow-up, 59% of Visudyne^®-treated patients with predominantly classic CNV had retained vision compared with 31% of placebo patients.⁶⁷

Severe vision loss (visual acuity loss of 6 lines or more) was also less likely with Visudyne^® therapy than with placebo. At both 12 and 24 months, a highly statistically significant 21–22% absolute difference was found between treatment groups for the percentage of patients with a visual acuity loss of less than 6 lines (p <0.001) (Figure 5.3).⁶⁷

Of the 105 patients with predominantly classic CNV at baseline, originally assigned to Visudyne^®, who completed the month 36 examination of the TAP Extension, 61 (58%) retained vision and only 13 (12%) had severe vision loss.⁷⁰

Above: Figures 5.2 and 5.3:
Figure 5.2 Percentage of eyes with a visual acuity loss of less than 3 lines through 24 months of the phase III TAP Investigation in AMD patients with predominantly classic CNV at baseline.
Figure 5.3 Percentage of eyes with a visual acuity loss of less than 6 lines through 24 months of the phase III TAP Investigation in AMD patients with predominantly classic CNV at baseline.

Visual acuity
Visual acuity either improved, or decreased by no more than 1 line, in 32% of Visudyne^® treated patients with predominantly classic CNV at month 24 compared with 18% of patients who received placebo (Figure 5.4).⁸⁴ Improvements of 3 lines or more were observed in 14 (9%) Visudyne^®-treated patients and 3 (4%) patients given placebo.

Figure 5.4 Mean change from baseline in visual acuity scores through 24 months of the phase III TAP Investigation in AMD patients with predominantly classic CNV at baseline.

Baseline best-corrected visual acuity was similar in both the Visudyne^® and placebo groups for patients with predominantly classic lesions in the TAP Investigation, and ranged from 20/40 to 20/200 (approximate Snellen equivalent) with a mean of 20/80–2 (10.5 lines or 52.7 letters on an ETDRS chart).⁶⁶ Visudyne^®-treated patients experienced a slower and smaller decline in visual acuity than patients who received placebo (Figure 5.5). Untreated patients lost as much visual acuity through 3 months as Visudyne^®-treated patients lost in 2 years. In both groups the decline was more rapid during the first 12 months, but became relatively stable between months 12 and 24. A treatment benefit was evident at each follow-up visit throughout the investigation, with Visudyne^®-treated patients losing about 2 fewer lines of visual acuity at 12 and 24 months compared with patients who received placebo (p <0.001).⁶⁷

Figure 5.5 Mean change from baseline in visual acuity scores through 24 months of the phase III TAP Investigation and 36 months of the TAP Extension in AMD patients with predominantly classic CNV at baseline.

Visual acuity in Visudyne^®-treated patients was less likely to deteriorate to a Snellen equivalent to 20/200 or worse by 24 months. This was despite both treatment groups sharing similar baseline characteristics, in particular a mean baseline visual acuity measuring 20/126. At 24 months, visual acuity reached 20/200 in 44% of Visudyne^®-treated patients and in 68% of patients given placebo (p <0.001).⁶⁷

The distribution of visual acuity scores remained relatively stable during the TAP Extension, with 50 (40%) of 124 and 45 (43%) of 105 Visudyne^®-treated patients having a visual acuity score of 20/200 or worse at the month 24 and month 36 examinations, respectively. The mean visual acuity letter score was 40 (Snellen equivalent 20/160) at month 24 and remained at 40 (20/160) at the month 36 examination.⁷⁰ A visual acuity improvement of atleast 3 lines of visual acuity was observed in 9 patients (9%). Initial analyses of data from the TAP Investigation confirmed the long-term durability (up to 5 years) of Visudyne^® in stabilizing vision and preventing further vision loss in patients.⁸⁵

Contrast sensitivity
Visual acuity is an important measure of visual function and the most frequently reported primary outcome measure in clinical trials of treatments for CNV. However, overall quality of vision depends on a number of factors and is best characterized by considering several measures.

Contrast sensitivity, a secondary vision outcome in the TAP Investigation and VIP Trial, is critical for detecting and discriminating between visual targets, such as faces, signs, clocks, traffic signals, and other everyday objects.^1,81 Retaining contrast sensitivity may be particularly important for patients who have already experienced a loss of visual acuity and the clinical benefits are most relevant for patients who have poorer visual acuity because tasks of daily living can be performed more easily with better contrast sensitivity, independent of visual acuity.

Throughout the TAP Investigation, mean contrast sensitivity scores were consistently better in patients treated with Visudyne^® therapy than in patients who received placebo. Visudyne^®-treated patients retained 6 more letters of contrast sensitivity (2 segments of contrast) at 24 months compared with placebo (Figure 5.6).^67,86 When the treatment groups were adjusted for age, study center, and baseline contrast sensitivity, there was a significant difference in contrast sensitivity scores between the treatment groups at both 12 and 24 months (p <0.001). Changes in contrast sensitivity scores paralleled the improvement in visual acuity scores, with a higher proportion of Visudyne^®-treated patients experiencing stable (an increase or decrease of 2 letters) or improved (an increase of 3 letters or more) contrast sensitivity scores compared with placebo (70% vs. 33%).

Angiographic outcomes
Angiographic outcomes provide independent and objective confirmation of visual function results. They also give some insight into possible biological mechanisms for the treatment effect.

The angiographic effects of Visudyne^® therapy are illustrated in Figure 5.7, which shows a case of predominantly classic CNV before Visudyne^® therapy and at follow-up 12 and 24 months after initiation of treatment. Visudyne^® therapy reduced leakage from classic CNV and restricted lesion growth in AMD patients with predominantly classic subfoveal CNV during the 24-month TAP Investigation.

Above Figures 5.6 and 5.7
Figure 5.6 Mean change from baseline in contrast sensitivity scores through 24 months of the phase III TAP Investigation in AMD patients with predominantly classic CNV at baseline.
Figure 5.7 Late-phase frames of fluorescein angiograms showing a predominantly classic lesion (a) before Visudyne therapy, (b) 12 months after treatment with Visudyne therapy, (c) 18 months after treatment with Visudyne therapy, and (d) 24 months after treatment with Visudyne therapy.

The distribution of angiographic gradings shown in Figure 5.8 indicates that Visudyne^® therapy reduced the progression of leakage from classic CNV, i.e. the area of leakage from classic CNV beyond the area of the entire lesion identified at baseline was reduced. This treatment effect was evident from as early as month 3 and was sustained through month 24. Visudyne^®-treated patients were more likely to have absence of leakage from classic CNV at month 24 than those given placebo (45% vs. 21%; p <0.001).67 Progression of leakage from classic CNV occurred in 29% of Visudyne^®-treated patients compared with 65% of patients who received placebo (p <0.001).⁶⁷

Figure 5.8 Grading of fluorescein leakage from classic CNV in AMD patients with predominantly classic CNV at baseline assessed using the TAP Angiographic Grading System at the month 24 examination in the phase III TAP Investigation.

Assessment of lesion size is an important measure of the magnitude of progression. Most lesion growth in patients with predominantly classic CNV in the TAP Investigation occurred during the first 12 months of the study, with negligible growth between months 12 and 24. Lesion size at the 24-month analysis was no greater than 6 MPS disc areas (3600 ?m) in 55% of Visudyne^®-treated patients, compared with 25% of those who received placebo (p <0.001) (Figure 5.9).⁸⁷ Conversely, a lesion size of greater than 6 MPS disc areas was observed in more patients who received placebo than Visudyne^® therapy (71% vs. 38%, p <0.001).⁶⁷

Figure 5.9 Distribution of lesion sizes at baseline and the month 24 examination in the phase III TAP Investigation in AMD patients with predominantly classic CNV at baseline.

Occult with no classic CNV in the VIP Trial

Chance of stabilized vision
Results in the 258 patients with occult with no classic CNV were similar to those observed in the overall population in the VIP Trial (n=339). By the month 24 examination, 75 (45%) Visudyne^®-treated patients retained vision (loss of less than 3 lines of visual acuity), compared with 29 (32%) patients given placebo (p = 0.032) (Figure 5.10a). Subgroup analyses suggested that the benefit of Visudyne^® therapy was greatest in patients presenting with either smaller lesions (≤4 MPS disc areas) or lower levels of visual acuity (letter score <65, approximate Snellen equivalent worse than 20/50) (Figure 5.10b). Of the 187 patients in this subgroup, 51% of Visudyne^®-treated patients retained vision at month 24 compared with 25% of placebo patients, with an absolute difference of 26% (p <0.001).⁶⁸

The risk of severe vision loss (visual acuity loss of 6 lines or more) at month 24 was greater in patients with occult with no classic CNV who received placebo (occurred in 47% of patients) than in those treated with Visudyne^® therapy (occurred in 29% of patients; p = 0.004). This difference was even more pronounced in the subgroup of patients with either smaller lesions or lower levels of visual acuity, in which 31 (48%) patients who received placebo had severe vision loss compared with 26 (21%) Visudyne^®-treated patients (p <0.001).⁶⁸

Visual acuity
The distribution of visual acuity change from baseline through the month 24 examination showed a benefit for patients with occult with no classic CNV treated with Visudyne^® therapy (Table 5.1). A treatment benefit in terms of mean visual acuity change from baseline was also observed: Visudyne^®-treated patients lost 3.8 lines compared with 5.1 lines in the placebo

Figure 5.10 Percentage of eyes that retained vision (loss of less than 3 lines of visual acuity at baseline) through 24 months of the phase IIIb VIP Trial in patients with AMD and (a) occult with no classic CNV or (b) occult with no classic CNV and either smaller lesions (≤4 MPS disc areas) or lower levels of visual acuity (letter score <65, approximate Snellen equivalent worse than 20/50).

group (p = 0.002). The corresponding results for the patients with either smaller lesions or lower levels of visual acuity were losses of 3.0 and 5.2 lines, for Visudyne^®-treated patients and patients given placebo, respectively (p <0.001).⁶⁸

Table 5.1: Frequency distribution of changes in visual acuity from baseline for patients with occult with no classic CNV

Visual acuity was less likely to decrease to 20/200 or worse in Visudyne^®-treated patients. This level was reached in 28% of Visudyne^®-treated patients, compared with 45% of patients given placebo (p = 0.006). This benefit was even more pronounced in patients with either smaller lesions or lower levels of visual acuity (24% vs. 50%; p <0.001).⁶⁸

Contrast sensitivity
The VIP Trial showed that Visudyne^® therapy preserved quality of vision by retaining visual acuity and stabilizing contrast sensitivity. Patients with occult with no classic CNV treated with Visudyne^® therapy in the VIP Trial lost less contrast sensitivity over 24 months than patients given placebo (mean number of letters of contrast sensitivity lost from baseline 3.7 vs. 6.1; p = 0.004).88 At month 24, 20% of Visudyne^®-treated patients and 34% of patients who received placebo had lost at least 9 letters of contrast sensitivity (p = 0.01). This benefit was also seen in the subgroup of patients with either smaller lesions or lower levels of visual acuity.⁸⁸

These results suggest that Visudyne^®-treated patients may be better able to perform visionrelated tasks than patients who received placebo, independent of their level of visual acuity.

Angiographic outcomes
In the VIP Trial, the subgroup of patients with occult with no classic CNV treated with placebo were about 2.5 times more likely to have lesions exceeding 9 MPS DA at the month 24 examination than those given Visudyne^® therapy. In addition, a higher percentage of placebotreated eyes developed evidence of classic CNV during the 24 months of the study (49% vs. 27%; p = 0.001). Progression of leakage from occult CNV was more common in patients given placebo at month 24 (57% vs. 46%; p = 0.12), but absence of leakage was more common in Visudyne^®-treated patients (42% vs. 29%; p = 0.04).⁶⁸

In the group of patients with either smaller lesions or lower levels of visual acuity, lesion size at month 24 was more likely to be smaller than 6 MPS DA in patients treated with Visudyne^® than in those given placebo (60% vs. 39%; p <0.001). In addition, the development of classic CNV in this patient group occurred less frequently in the Visudyne^®-treated patients compared with those given placebo (25% vs. 52%; p <0.001).⁶⁸

Improving outcomes in occult with no classic CNV – the VALIO Study
The phase I/II dose-finding studies for Visudyne^® therapy were conducted mainly in patients with classic-containing CNV. Therefore, it is feasible that the treatment regimen was not optimal for patients with occult with no classic CNV. The VALIO Study investigated the benefits of delaying light application in these patients, which in theory could benefit patients by increasing the selectivity of the photodynamic therapy (there is 50% less Visudyne^® in the choroidal circulation 30 minutes after infusion compared with 15 minutes after infusion).

No difference in angiographic or vision outcomes between the standard and delayed light regimens was identified through 6 months of follow-up.⁸⁹ At present, the standard regimen of Visudyne^® therapy is still recommended when considering treatment of occult with no classic CNV. The VALIO Study is currently ongoing through 12 months.

No statistically significant treatment effect, in terms of at least 3 lines of visual acuity loss, was observed for AMD patients with minimally classic CNV through 24 months of the TAP Investigation.⁶⁷ However, these patients did experience treatment benefits for most secondary visual and angiographic outcomes including contrast sensitivity, although the magnitude of the benefits was not as great as for patients with predominantly classic CNV.^84,86

After 12 months of follow-up in the VIM Trial, patients treated with Visudyne^® therapy (with either reduced light fluence or standard light fluence) had significantly better vision outcomes than patients given placebo. The mean change in visual acuity scores of patients treated with Visudyne^® therapy was better in each group compared with patients receiving placebo (reduced fluence p=0.02; standard fluence p=0.08).⁸⁵ In addition, patients given Visudyne^® had an increased chance of stable or improved vision compared with placebo.⁹⁰

Patients with minimally classic CNV treated with Visudyne^® therapy in the VIM Trial had better angiographic outcomes than those given placebo. Specifically, fewer Visudyne^®-treated patients developed predominantly classic CNV compared with placebo.⁸⁵ Further follow-up is required before any conclusions can be drawn from this study.

Visudyne^® therapy appeared to be as or more beneficial in Japanese patients enrolled in JAT than Caucasian AMD patients, when results from JAT were compared with historic angiographic data from the TAP Investigation. The primary outcome measure in JAT was defined as progression of leakage from classic CNV. At the month 12 examination in JAT, 12 (19%) patients had progression of leakage from classic CNV, and only 9 (14%) patients had progression of leakage from occult CNV. The safety profiles between the two studies were similar.⁷⁷

This section concentrates on the results from the pathologic myopia arm of the phase IIIb VIP Trial. In contrast to patients with neovascular AMD, there is no evidence that lesion composition significantly affects treatment outcomes in patients with CNV secondary to pathologic myopia.

After completion of the 24 months of the VIP Trial, patients with pathologic myopia were invited to participate in the VIP Extension.

Quality of vision depends on several aspects of visual function, such as visual acuity and contrast sensitivity. The overall results from 24 months of the pathologic myopia arm of the VIP Trial showed that Visudyne^® therapy retained quality of vision by reducing the risk of visual acuity loss through 12 months and stabilizing or improving visual acuity and contrast sensitivity through 24 months. In the first 12 months of the extension of the VIP Trial, these treatment benefits were maintained, demonstrating the long-term beneficial effect in these patients.⁷¹

The results through 24 months of the VIP Trial showed that stable vision (a loss of less than 8 letters or 1.5 lines of visual acuity) was more frequent with Visudyne^® therapy than with

Figure 5.11 Percentage of eyes with a visual acuity loss of less than 8 letters (approximately 1.5 lines) from baseline through the first 12 months of the phase IIIb VIP Trial in patients with pathologic myopia.

Visudyne^® therapy significantly reduced the risk of at least 3 lines of visual acuity loss in patients with subfoveal CNV secondary to pathologic myopia at the month 12 examination, but the effect was no longer statistically significant at the month 24 examination. At 12 months, 70 (86%) Visudyne^®-treated patients had lost less than 3 lines of visual acuity compared with 26 (67%) patients who received placebo (p = 0.011).³⁵ At 24 months, 64 (79%) Visudyne^®-treated patients and 28 (72%) patients who received placebo lost less than 3 lines of visual acuity (p = 0.38).⁶⁹

There are several possible reasons for the loss of statistical significance for the measures of stable vision and at least 3 lines of visual acuity loss by the month 24 follow-up examination. The primary endpoints set out in the trial were dichotomous variables, for which a change of just 1 letter in visual acuity could alter a patient’s response from success to failure or vice versa. In addition, the 2:1 randomization in this study resulted in a small number of patients in the placebo group. This meant that if even a few patients had a response inconsistent with the natural progression of the disease, the effect on the responder rate could be considerable. When the evidence is considered as a whole, taking into account the results of the secondary endpoints, the overall therapeutic effect is still evident over the 24-month period.

Baseline best-corrected visual acuity, measured using an ETDRS chart, was similar for both treatment groups, with a median of 20/64±2 and 20/64-2, respectively, for Visudyne^® and placebo groups. A treatment benefit compared with placebo was observed at each follow-up visit (Figure 5.12).⁶⁹ At the month 12 follow-up, the median visual acuity of the Visudyne^® treated group was stable, while patients given placebo had lost almost 2 lines of visual acuity (p = 0.01).³⁵ This benefit was maintained at month 24, by which point the median visual acuity of the Visudyne^®-treated and placebo groups had changed from baseline by +0.2 lines and –1.6 lines, respectively (p = 0.05).⁶⁹ A treatment benefit was also evident at month 24, when Visudyne^®-treated patients had a higher median visual acuity (20/64+1) than patients given placebo (20/100+1) (p = 0.07).⁶⁹

Figure 5.12 Median change from baseline in visual acuity scores through 24 months of the phase IIIb VIP Trial in
patients with pathologic myopia.

At month 12, approximately three times as many patients given placebo had visual acuity scores of 20/200 or worse (defined as legal blindness if it occurs in the better-seeing eye), compared with Visudyne^®-treated patients, at month 12 (18% vs. 6%; p = 0.04).³⁵

Vision was unchanged (increase or decrease of <1 line) or improved (increase of ≥1 line) at month 24 in 44 (54%) Visudyne^®-treated patients compared with 17 (44%) patients given placebo (Figure 5.13).⁶⁹ In contrast to patients with CNV due to AMD, a large percentage of patients with CNV due to pathologic myopia had an increase in visual acuity after treatment with Visudyne^®. Three times as many Visudyne^®-treated patients than patients given placebo had an improvement from baseline of at least 1 line of visual acuity (39% vs. 13%, p = 0.003), and improvements of at least 3 lines occurred in 10 (12%) Visudyne^®-treated and no placebo patients (p = 0.029). In contrast, decreases in vision of 3 lines or more, which are clinically relevant as they represent a doubling of the visual angle, occurred in fewer Visudyne^®-treated patients (17, 21%) than patients who received placebo (11, 28%).⁶⁹

Figure 5.13 Distribution of changes in visual acuity scores at the month 24 examination, compared with baseline, in the phase IIIb VIP Trial in patients with pathologic myopia.

Contrast sensitivity

Visudyne^® therapy improved quality of vision in patients with pathologic myopia by stabilizing contrast sensitivity as well as improving visual acuity outcomes. Patients with stabilized contrast sensitivity are more likely to retain their ability to perform vision-related tasks. Contrast sensitivity remained stable in Visudyne^®-treated patients with pathologic myopia through 24 months of the VIP Trial while a slight deterioration was observed in the placebo group.⁶⁹ Contrast sensitivity was stabilized (increase or decrease of up to 2 letters) or improved (increase of 3 or more letters) in 54 (74%) of 73 Visudyne^®-treated patients and 23 (68%) of 34* placebo recipients.⁹¹

The majority of patients (96%) with pathologic myopia in the VIP Trial had evidence of classic CNV at baseline; only 15% of patients had occult CNV. At month 24, the overall distribution of closure gradings was not significantly different between the two treatment groups. However, angiographic gradings showed that Visudyne^®-treated patients were less likely to have progression of leakage from classic CNV than patients who received placebo, with an 12% difference between treatment groups at month 24 (p = 0.22).⁶⁹

Lesion size tended to be much smaller in patients with pathologic myopia in the VIP Trial than in patients with AMD in the TAP Investigation or VIP Trial. At baseline, 63% of Visudyne^® treated patients and 56% of patients who received placebo had a lesion size no greater than 1 MPS disc area (diameter 1500 ?m) (Figure 5.14).³⁵ No Visudyne^®-treated lesion exceeded 6 MPS disc areas at any time during the 24 months of the study and the distribution of lesion sizes at baseline, month 12, and month 24 was similar. However, lesion size tended to increase in patients who received placebo; almost half as many patients had a lesion size of 1 MPS disc area or less at month 24 compared with baseline (36% vs. 56%, p = 0.05), and the proportion of patients with lesions greater than 3 MPS disc areas almost tripled from 10% at baseline to 28% at month 24 (p = 0.01).^35,69
_{*Contrast sensitivity data in the placebo group were only available for 34 of the 39 patients}

Figure 5.14 Distribution of lesion sizes at baseline and month 24 in the phase IIIb VIP Trial in patients with pathologic myopia

The ocular histoplasmosis syndrome

Visudyne^® therapy was evaluated in 26 patients with CNV secondary to OHS in the openlabel, uncontrolled VOH Study.^74,75 Although primarily intended to investigate the safety of Visudyne^® therapy, the VOH Study also included analyses of vision and angiographic outcomes. Four patients discontinued from the study due to violation of inclusion/exclusion criteria, non-compliance, loss to follow-up, or death.⁹²

Visual acuity
The VOH Study showed that the majority of patients who received Visudyne^® therapy had improvements in visual acuity at each successive 3-month examination. At the 24-month examination, Visudyne^®-treated patients had gained a median of 1.2 lines (6.0 letters) of visual acuity.75 Of the 22 patients in the study at month 24, ten gained at least 1.4 lines (7 letters) of visual acuity. Four patients lost at least 1.6 lines (8 letters), of which two lost at least 3 lines (15 letters). These results compare favorably with the natural history of the disease; in a retrospective study of 74 eyes with OHS, 28% improved or lost less than 2 lines and 61% lost 4 or more lines after a median follow-up of 36.5 months.⁴³

Contrast sensitivity
Contrast sensitivity outcomes in the VOH Study were similar to those for visual acuity; mean contrast sensitivity improved at each visit. At the 24-month examination, 16 Visudyne^®-treated patients gained at least 3 letters of contrast sensitivity and one lost at least 3 letters, while five patients had no change.⁷⁵

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