Verteporfin Treatment Research Articles

Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age-related macular degeneration

This open-label, prospective, small-scale study investigated the benefits of same-day verteporfin and intravitreal ranibizumab in patients with predominantly classic, minimally classic or occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. Patients received verteporfin at baseline and at month 3, if leakage persisted. Ranibizumab (0.5 mg) was given at baseline and months 1, 2 and 3, and thereafter at monthly intervals if required. Same-day ranibizumab was given ≥ 1 hr after verteporfin. Fifteen patients [11 male, four female; mean age 75.5 years (range 54-94 years)] were treated. At day 360, mean visual acuity (VA) had improved by 10.9 letters. An increase of ≥ 15 and ≥ 30 letters (i.e. ≥ 3 and ≥ 6 lines) was observed in seven (47%) patients and one patient (7%), respectively. Mean central retinal thickness (CRT) decreased by 85 μm. At days 7, 14 and 30, CNV perfusion was absent in 14/15 patients. Mean lesion area had reduced from baseline by 23.1% at day 120, 25.5% at day 180 and 23.6% at day 360. There were no visual safety concerns and intraocular pressures remained normal. Only two serious adverse events were recorded over the 12-month period, and neither was considered to be related to treatment. Same-day verteporfin plus ranibizumab improved VA, reduced CRT, prevented CNV perfusion and reduced lesion area safely over 12 months. Further investigation is warranted to confirm whether this combination improves long-term vision and reduces the need for retreatment.

ANTI-VEGF DRUGS AS THE 2009 FIRST-LINE THERAPY FOR CHOROIDAL NEOVASCULARIZATION IN PATHOLOGIC MYOPIA

Pathologic myopia is the second cause of choroidal neovascularization, after age-related macular degeneration (AMD), and the first cause in patients younger than 50 years. The current treatment of subfoveal myopic choroidal neovascularization (mCNV) is verteporfin photodynamic therapy, but its long-term effectiveness has been disappointing. Antivascular endothelial growth factor (anti-VEGF) drugs are now widely used not only to treat choroidal neovascularization in AMD but also for choroidal neovascularization in other conditions. This review summarizes the data supplied by published case series studies about anti-VEGF therapy in mCNV. Analysis of the current literature allowed discussion of the optimal parameters for mCNV treatment by anti-VEGF, including the choice of anti-VEGF drug, its dose, the treatment protocol, and indications for retreatment. To date, the results of intravitreal bevacizumab or ranibizumab for mCNV have been reported in at least 14 studies, but they were all pilot, monocentric, and noncomparative case series. Nevertheless, they provided useful information on >250 patients and showed similar results, with significant improvement of visual acuity and an excellent safety profile. Shifting from one treatment to another is always difficult in the absence of prospective and controlled comparative studies. However, in 2009, intravitreal ranibizumab or bevacizumab may be considered as first-line therapy for sub- and juxtafoveal mCNV for three reasons: the safety of anti-VEGF drugs and intravitreal injection procedures; the disappointing long-term results of other therapies, including verteporfin treatment; and the excellent convergent results of anti-VEGF therapy in all pilot studies.

Combination of verteporfin photodynamic therapy and ranibizumab: effects on retinal anatomy, choroidal perfusion and visual function in the protect study

Objective:To evaluate verteporfin and same-day ranibizumab on retina, choroid, vasculature, choroidal neovascularisation (CNV) and visual function.Methods:Eleven patients with occult or predominantly classic subfoveal CNV secondary to age-related macular degeneration received...

Management of choroidal neovascularization in myopic macular degeneration

Choroidal neovascularization (CNV) is one of the most important vision-threatening complications secondary to pathological myopia (PM). In the last 20 years, there have been rapid advances in the treatment options for myopic CNV. The aim of this article is to give an overview of several modalities of treatment of CNV in myopes, including laser photocoagulation, transpupillary thermotherapy, radiotherapy, photodynamic therapy with verteporfin and surgical treatments. Based on the scientific progress achieved in the past few years, it is possible that patients with myopic macular degeneration complicated by CNV may benefit from a new ophthalmic frontier of pharmacologic therapy, including intravitreal injections of anti-VEGF drugs. The current status of these novel therapeutic agents is also discussed.

EFFECT OF ADJUNCTIVE DICLOFENAC WITH VERTEPORFIN THERAPY TO TREAT CHOROIDAL NEOVASCULARIZATION DUE TO AGE-RELATED MACULAR DEGENERATION

To determine short-term effects of topical diclofenac administered in conjunction with verteporfin therapy for predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). Randomized, multicenter (14), prospective, placebo-controlled, double-masked clinical trial. Patients (n=61) were randomly assigned to treatment with diclofenac sodium ophthalmic solution 0.1% or placebo and followed for 12 weeks. Patients instilled diclofenac or placebo two drops four times daily, 2-4 days before verteporfin treatment until 2 weeks after treatment, then two drops twice daily for 10 weeks. This exploratory study was not powered to detect differences between treatment groups. Statistical analyses were conducted solely to aid interpretation of results. In diclofenac-treated eyes, mean changes in visual acuity letter score from baseline in the diclofenac and placebo groups were +1.8 letters and -1.0 at week 1 (P=0.505 between groups). Mean visual acuity letter scores decreased in both groups at all subsequent visits, with a mean change at 12 weeks of -7.4 with diclofenac and -2.6 with placebo (P=0.213). Percentages of eyes with stable or improved vision (change <or=4 or increase >or=5 letters) were similar in the diclofenac and placebo groups at all study visits. No significant between-group differences in changes from baseline in lesion area, greatest linear dimension (GLD), fluorescein leakage, or retinal thickness were detected. In patients with predominantly classic subfoveal CNV due to AMD, administration of topical diclofenac with verteporfin therapy was associated with similar vision outcomes to placebo plus verteporfin therapy.

Four-month back pain after verteporfin treatment: clinical case notes.

To describe the case of a patient with long-term back pain post verteporfin injection for photodynamic therapy. Clinical case description from a metropolitan ophthalmic practice. Following injection of verteporfin, the patient developed continuous severe back pain. The back pain resolved over 4 months, and despite thorough orthopaedic and neurologic work-up, no other explanation was found. The temporal association of pain with verteporfin treatment, combined with a failure to identify an alternate cause, led the authors to attribute the patient's back pain to photodynamic therapy treatment.

Large Submacular Hemorrhage Following PDT With Verteporfin in Patients With Occult CNVM Secondary to Age-Related Macular Degeneration

A review of the charts for all patients who developed large submacular hemorrhages following photodynamic therapy for choroidal neovascular membranes secondary to age-related macular degeneration yielded three patients who met the criteria for a large submacular hemorrhage. All three patients were treated for exudative age-related macular degeneration and were taking warfarin for chronic anticoagulation. Before photodynamic therapy, the international normalized ratio ranged from 1.2 to 1.6. All three patients had received at least one previous verteporfin treatment in the study eye. All three hemorrhages were not noted immediately after photodynamic therapy and were documented within 1 to 2 weeks following the procedure. Patients with age-related macular degeneration who are receiving warfarin therapy and undergoing repeat verteporfin treatments appear to be at risk for submacular hemorrhages.

Using contrast sensitivity to estimate the cost-effectiveness of verteporfin in patients with predominantly classic age-related macular degeneration

To re-evaluate the cost-effectiveness of photodynamic therapy with verteporfin (Visudyne, Novartis AG, Switzerland) in patients with predominantly classic and classic choroidal neovascularization (CNV) owing to age-related macular degeneration (AMD), using new evidence on the impact of contrast sensitivity on health status. A health economic model is used to synthesise the evidence on contrast sensitivity and treatment rates from the TAP Investigation with health state utilities and costs. Impairment of visual function is estimated using a Markov model to predict transitions between states of contrast sensitivity. Each state is associated with costs and a health state utility. Total expected costs and benefits for a cohort of patients over a defined number of cycles are calculated. The expected health state utility for each disease state was estimated using results from a study of 209 patients with AMD in Sheffield. The model includes the costs associated with treatment and monitoring in the verteporfin treatment arm and costs offset by delaying the deterioration of visual function. Beyond 3 years, the annual costs of the verteporfin arm are estimated to be less than the annual costs of the control arm, owing to the cost associated with higher blindness prevalence in the control arm. Over time, the results show that both the incremental utility and cost decreases. By 10 years, the estimated incremental cost-effectiveness is approximately pound20 996 per Quality-Adjusted Life Years. The results of this study suggest that the verteporfin therapy in the treatment for patients with predominantly classic and classic CNV owing to AMD is encouraging.

Photodynamic Therapy With Verteporfin and Intravitreal Triamcinolone Acetonide in the Treatment of Neovascular Age-related Macular Degeneration

To examine the efficacy of photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide in the treatment of neovascular age-related macular degeneration (AMD). Retrospective, interventional case series. Sixty eyes of 56 patients with neovascular AMD were treated with PDT with verteporfin followed by an intravitreal injection of 4 mg triamcinolone acetonide. The main outcome measures were visual acuity (VA), retreatment frequency with PDT (and triamcinolone), and frequency of side effects. Mean follow-up was 15.9 months (range 12 to 30 months, median 15 months). Twenty-three (38.3%) of 60 eyes had a stable result at 12 months' follow-up (that is, loss/gain <three lines) and 34 (56.7%) of 60 had a loss of 3 lines or more. Three patients (5%) had an improvement of 3 lines or more. Lesion type, patient age, and lesion size had no influence on the outcome, but baseline VA had a statistically significant effect (P = .006). The median number of PDT-intravitreal triamcinolone acetonide treatments was one. One-third (20 of 60) of all eyes had an increase in intraocular pressure (IOP) that required therapy. There were no cases of endophthalmitis, but 13 patients (21.6%) developed severe cataract that required surgery. The combination of PDT and intravitreal triamcinolone acetonide requires careful consideration as a treatment option for neovascular AMD. In our case series, this treatment combination did not prevent a considerable decrease in VA. The main benefit of this combination treatment was a low number of verteporfin treatments. Baseline VA was the main predictor of the final outcome.

Verteporfin Therapy of Subfoveal Minimally Classic Choroidal Neovascularization in Age-Related Macular Degeneration

To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration. Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial. Nineteen ophthalmology practices in North America and Europe. Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas. We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300 mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis. One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF. Verteporfin therapy safely reduced the risks of losing at least 15 letters (> or =3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial.

Effect of Tumor Host Microenvironment on Photodynamic Therapy in a Rat Prostate Tumor Model

Tumor host microenvironment plays an important role in tumor growth, metastasis, and response to cancer therapy. In this study, the influence of tumor host environment on tumor pathophysiology, photosensitizer distribution, and photodynamic therapy (PDT) treatment effect was examined in the metastatic at lymph node and lung (MatLyLu) rat prostate tumor. MatLyLu tumors implanted in different host environment [i.e., orthotopically (in the prostate) or s.c.] were compared for difference in vessel density, average vessel size, vascular permeability, tumor vascular endothelial growth factor production, and tumor oxygenation. Uptake of photosensitizer verteporfin in tumors in both sites was determined by fluorescence microscopy. To compare tumor response to PDT, both orthotopic and s.c. MatLyLu tumors were given the same doses of verteporfin and laser light treatment, and PDT-induced tumor necrotic area was measured histologically. Orthotopic MatLyLu tumors were found to grow faster, have higher vessel density and more permeable vasculature, have higher vascular endothelial growth factor protein levels, and have lower tumor hypoxic fraction than the s.c. tumors. Uptake of photosensitizer verteporfin in the orthotopic tumor was higher than in the s.c. tumors at 15 minutes after injection (1 mg/kg, i.v.), and became similar at 3 hours after injection. For the vascular targeting PDT treatment (0.25 mg/kg verteporfin, 50 J/cm(2) at 50 mW/cm(2), 15 minutes drug-light interval), there was no significant difference in PDT-induced tumor necrotic area between the orthotopic and s.c. tumors, with 85% to 90% necrosis in both types of tumors. However, tumor necrosis induced by the cellular targeting PDT (1 mg/kg verteporfin, 50 J/cm(2) at 50 mW/cm(2), 3 hours drug-light interval) was significantly different in the orthotopic (64%) versus the s.c. (29%) tumors. Tumor host environment can significantly affect photosensitizer verteporfin distribution and PDT treatment effect. Verteporfin-PDT regimen targeting tumor cells is more sensitive to such influence than the vascular targeting PDT. Our study showed the importance of tumor host environment in determining tumor physiologic properties and tumor response to PDT. To obtain clinically relevant information, orthotopic tumor model should be used in the experimental studies.

Changes in neovascular membranes and normal choroid blood vessels after multiple photodynamic therapy treatments

ICG angiography (ICGA) was used to document the effect of repeated PDT (verteporfin) on size and leakage of choroidal neovascularisation in age-related macular degeneration (AMD) and treatment-related side effects on the choroid. Forty-two patients were followed over 24 months in a clinical trial for PDT in AMD. The ICGAs were performed every 3 months with a confocal laser scanning system. Patients received repeated verteporfin treatment. At each control visit, the patients were retreated if leakage was present in fluorescein angiography (FA). A continuous, highly significant reduction in CNV size and leakage area was found over 24 months. The initial CNV size dropped by 23% from 3.86 mm2 to 2.98 mm2. The leakage area in the late phase of the angiogram decreased by 30.3% from 5.0 mm2 to 3.5 mm2. A significant side effect of PDT on the choroid was documented by an increased hypofluorescent area in ICGA. The maximum size of the hypofluorescent area was reached after 12 months. At month 24, the choroidal fluorescence showed recovery in respect to area and intensity of fluorescence. But hypofluorescence surrounding the CNV lesion was already present in 40 out of 42 eyes before treatment. The ICGA confirms that repeated PDT treatments lead to a significant reduction in CNV size and leakage area over as long as 2 years. CNV lesions are surrounded by choriocapillary hypofluorescence in ICGA. PDT causes further hypoperfusion of the choroid but in the long-term significant recovery of choroidal perfusion was shown.

LASER TREATMENTS WITH VERTEPORFIN THERAPY AND ITS POTENTIAL IMPACT ON RETINAL PRACTICES

In the 1990s, the only available treatment for neovascular age-related macular degeneration (ARMD) was laser photocoagulation, but a minority of patients could be treated. Photodynamic therapy with verteporfin potentially allows many more patients to be treated. The authors' aim was to assess the impact of this increase on retinal practices. The number of patients who received laser photocoagulation in 1998 was determined. Based on that number and a retrospective review of 1000 consecutive records of new patients with ARMD referred to the Associated Retinal Consultants practices during 1998, estimates were made of how many patients would have been eligible for verteporfin therapy. Of the 1000 patients, 171 had predominantly classic subfoveal choroidal neovascularization secondary to ARMD and would have been eligible for verteporfin therapy, compared with 99 treated with laser photocoagulation according to Macular Photocoagulation Study guidelines. If this patient population is representative of the general population, approximately 84,000 patients would be eligible for verteporfin therapy in the United States per year, compared with 42,000 for laser photocoagulation. This would lead to 286,000 verteporfin treatments per year if retreatments are required. This increase in treatments for neovascular ARMD will have a considerable impact on retinal practices. Although the resources that will need to be expended are high, the potential benefit of verteporfin therapy in reducing vision loss will outweigh the costs.

LASER TREATMENTS WITH VERTEPORFIN THERAPY AND ITS POTENTIAL IMPACT ON RETINAL PRACTICES

Background: In the 1990s, the only available treatment for neovascular age-related macular degeneration (ARMD) was laser photocoagulation, but a minority of patients could be treated. Photodynamic therapy with verteporfin potentially allows many more patients to be treated. The authors' aim was to assess the impact of this increase on retinal practices. Methods: The number of patients who received laser photocoagulation in 1998 was determined. Based on that number and a retrospective review of 1000 consecutive records of new patients with ARMD referred to the Associated Retinal Consultants practices during 1998, estimates were made of how many patients would have been eligible for verteporfin therapy. Results: Of the 1000 patients, 171 had predominantly classic subfoveal choroidal neovascularization secondary to ARMD and would have been eligible for verteporfin therapy, compared with 99 treated with laser photocoagulation according to Macular Photocoagulation Study guidelines. If this patient population is representative of the general population, approximately 84,000 patients would be eligible for verteporfin therapy in the United States per year, compared with 42,000 for laser photocoagulation. This would lead to 286,000 verteporfin treatments per year if retreatments are required. Conclusions: This increase in treatments for neovascular ARMD will have a considerable impact on retinal practices. Although the resources that will need to be expended are high, the potential benefit of verteporfin therapy in reducing vision loss will outweigh the costs.