Physicians' concerns towards prescription adherence and treatment effectiveness in the clinical management of actinic keratosis.

AIM: We report concerns toward prescription adherence and treatment effectiveness in the clinical management of actinic keratosis (AK) in Italy. METHODS: We carried out a cross-sectional web-based survey among Italian dermatologists across Italy. Physicians were asked to answer a self-administered questionnaire about their concerns around AK therapy and barriers to patients' adherence. Each physician also profiled his last patient and answered items concerning his experience with topical treatments and the suitability of current and future treatment options for the profiled patient. RESULTS: Fifty practitioners answered the survey. Most dermatologists agreed that field-therapy is a key element for the management of AK in most patients, and 76% (N.=38) agreed that topical treatments were the best option in such cases given their ability to target subclinical lesions. However most interviewee underlined the importance of fostering patients' adherence and minimizing side effects in order to maximize benefits from therapy. CONCLUSION: We showed that features of current therapeutic options for field-directed therapy (namely long duration of treatment, intensity and duration of local skin reaction) raise practitioners' concerns toward patients' prescription adherence and real-world effectiveness.

Treatment patterns for neovascular age-related macular degeneration: analysis of 284 380 medicare beneficiaries.

PURPOSE: To examine trends in the treatment of newly diagnosed neovascular age-related macular degeneration (AMD). DESIGN: Retrospective cohort study. METHODS: Among 284 380 Medicare beneficiaries with a new diagnosis between 2006 and 2008, we used the cumulative incidence function to estimate procedure rates and the mean frequency function to estimate the cumulative mean number of intravitreous injections. We used Cox log-binomial regression to estimate predictors of the use of vascular endothelial growth factor (VEGF) antagonists within 1 year after diagnosis. Discontinuation of anti-VEGF therapy was defined by absence of treatment for 12 months. Discontinuation rates were calculated using the Kaplan-Meier method. RESULTS: The proportion of patients receiving anti-VEGF therapy increased from 60.3% to 72.7%, photodynamic therapy decreased from 12.8% to 5.3%, and thermal laser treatment decreased from 5.5% to 3.2%. Black patients (hazard ratio, 0.77; 95% confidence interval, 0.75-0.79) and patients of other/unknown race (0.83; 0.81-0.84) were less likely than white patients to receive anti-VEGF therapy. Patients with dementia were less likely to receive anti-VEGF therapy (0.88; 0.88-0.89). Among patients who received anti-VEGF therapy, the mean number of injections within 1 year of the first injection was 4.3 per treated eye. Anti-VEGF therapy was discontinued in 53.6% of eyes within 1 year, and in 61.7% of eyes within 18 months. CONCLUSIONS: Treatment of new neovascular AMD changed significantly between 2006 and 2008, most notably in the increasing use of anti-VEGF therapies. However, few patients treated with anti-VEGF medications received monthly injections, and discontinuation rates were high.

How tissue optics affect dosimetry of photodynamic therapy.

We describe three lessons learned about how tissue optics affect the dosimetry of red to near-infrared treatment light during PDT, based on working with Dr. Tayyaba Hasan. Lesson 1-The optical fluence rate φ near the tissue surface exceeds the delivered irradiance (E). A broad beam penetrates into tissue to a depth (z) as φ=Eke(-µz), with an attenuation constant µ and a backscatter term k. In tissues, k is typically in the range 3-5, and 1∕µ equals δ, the 1∕e optical penetration depth. Lesson 2-Edge losses at the periphery of a uniform treatment beam extend about 3δ from the beam edge. If the beam diameter exceeds 6δ, then there is a central zone of uniform fluence rate in the tissue. Lesson 3-The depth of treatment is linearly proportional to δ (and the melanin content of pigmented epidermis in skin) while proportional to the logarithm of all other factors, such as irradiance, exposure time, or the photosensitizer properties (concentration, extinction coefficient, quantum yield for oxidizing species). The lessons illustrate how tissue optics play a dominant role in specifying the treatment zone during PDT.

Integrating spheres for improved skin photodynamic therapy.

The prescribed radiant exposures for photodynamic therapy (PDT) of superficial skin cancers are chosen empirically to maximize the success of the treatment while minimizing adverse reactions for the majority of patients. They do not take into account the wide range of tissue optical properties for human skin, contributing to relatively low treatment success rates. Additionally, treatment times can be unnecessarily long for large treatment areas if the laser power is not sufficient. Both of these concerns can be addressed by the incorporation of an integrating sphere into the irradiation apparatus. The light fluence rate can be increased by as much as 100%, depending on the tissue optical properties. This improvement can be determined in advance of treatment by measuring the reflectance from the tissue through a side port on the integrating sphere, allowing for patient-specific treatment times. The sphere is also effective at improving beam flatness, and reducing the penumbra, creating a more uniform light field. The side port reflectance measurements are also related to the tissue transport albedo, enabling an approximation of the penetration depth, which is useful for real-time light dosimetry.

Cataract surgery is associated with a higher rate of photodynamic therapy for age-related macular degeneration.

PURPOSE: To investigate the association between cataract surgery and the rate of photodynamic therapy (PDT) for age-related macular degeneration (AMD). DESIGN: Observational population-based retrospective case-control study. PARTICIPANTS: All members in a district of the largest health maintenance organization (HMO) in Israel > 50 years old on January 1, 2001, who did not terminate their membership through May 31, 2005 (139 894 members). METHODS: All PDT procedures for AMD performed in the study population between January 1, 2001 and May 31, 2005 (283 patients) and all cataract surgeries performed between January 1, 2001 and December 31, 2003 (5913 patients) were documented. We extracted clinical information from the chronic disease registry of the HMO as well as demographic and socioeconomic information. For each patient that underwent cataract surgery, 5 HMO members matched in age, gender, chronic diseases (systemic hypertension, diabetes, hyperlipemia, and ischemic heart disease), place of residence, country of birth and socioeconomic status, who did not undergo cataract surgery, were randomly chosen as controls (n = 29 565). MAIN OUTCOME MEASURES: The rate for undergoing PDT at different time periods after cataract surgery. RESULTS: Fifty (0.85%) cataract patients and 94 control cases (0.32%) underwent PDT after cataract surgery (P<0.0001, chi-square test). A significant rise in PDT rate was noticed in cataract patients compared to controls during the first 6 months after surgery (P = 0.004, chi-square test). Between 6 and 12 months postoperatively, the PDT rates were similar in both groups. However, a more significant rise in PDT rates occurred between 1 and 1.5 years after surgery (P<0.0001, chi-square test). The Kaplan-Meier PDT-free survival curve of cataract patients was significantly worse than that of the controls (P<0.0001, chi-square test; P = 33.7, log-rank test). The hazard ratio for cataract patients compared to controls to undergo PDT after surgery was 2.7 (confidence interval = 2.4-5.7). The most significant factors to reduce the time to PDT were advanced age followed by having had cataract surgery, place of birth, socioeconomic status, and hyperlipidemia (Cox proportional hazards survival regression). CONCLUSIONS: We identified an increased rate of PDT, presumably for subfoveal AMD, 1 to 1.5 years after cataract surgery.

Towards conformal light delivery using tailored cylindrical diffusers: attainable light dose distributions.

Interstitial light delivery for therapeutic applications requires the use of fibre-based light diffusers. Such diffusers are presently manufactured to emit with a flat longitudinal power profile. Recently, diffusers with tailored longitudinal emission profiles have become available opening an avenue to improve conformal light delivery. This paper explores the ability of tailored diffusers to improve light dose confinement to the target volume. A formalism to calculate the light dose from an arbitrary source distribution is presented based on the convolution with an appropriate point source function. By choosing a source distribution corresponding to a cylindrical diffuser emitting with a sinusoidal profile, the set of attainable light dose distributions is characterized via a relationship between the diffuser's spatial frequency, the radial distance and the amplitude of the isodose contour.

Risk factors for photodynamic therapy of predominantly classic choroidal neovascularization in age-related macular degeneration.

PURPOSE: To investigate the influence of various risk factors for age-related macular degeneration (AMD) on the rate of undergoing photodynamic therapy (PDT). DESIGN: An observational population based cohort study. SETTINGS: A district of the largest health maintenance organization (HMO) in Israel. STUDY POPULATION: All HMO members in the district, older than 50 years on January 1, 2001, who did not terminate their membership until May 31, 2005 (139,894 members); of those, 283 underwent PDT for AMD during the study period (775 procedures). OBSERVATION PROCEDURES: We extracted information from the chronic disease registry of the HMO as well as demographic information including age, gender, country of birth, place of residency, and social security economic status. MAIN OUTCOME MEASURES: Effect of various risk factors for AMD on the rate of PDT. RESULTS: The age-adjusted proportion of patients requiring PDT was significantly higher in hypertensives (P = .03, chi2 test), in hyperlipidemics (P = .002), in ischemic heart disease patients (P = .002) and among males (P = .03) and Ashkenazi Jews (P = .02). No significant difference in PDT rates was noted in diabetics, congestive heart failure (CHF), and chronic renal failure (CRF) patients. PDT rates were lower in the lower socioeconomic class (P = .002). Logistic regression found a significant effect of age, hyperlipidemia, hypertension, socioeconomic status, and gender on the rate of PDT, while ischemic heart disease (IHD), diabetes, CHF, CRF, place of birth, and place of residence did not contribute significantly to the model. CONCLUSIONS: Advanced age, hypertension, hyperlipidemia, male gender, and socioeconomic status are risk factors for undergoing PDT for predominantly classic neovascular AMD.

Trends in provision of photodynamic therapy and clinician attitudes: a tracker survey of a new health technology.

BACKGROUND: There has been debate about the cost-effectiveness of photodynamic therapy (PDT), a treatment for neovascular age-related macular degeneration. We have been monitoring trends for the provision of PDT in the UK National Health Service. The fourth annual 'tracker' survey took place as definitive National Institute for Clinical Excellence (NICE) guidance was issued. We assessed trends in PDT provision up to the point of release of the NICE guidance and identified likely sources of pressure on ophthalmologists to provide PDT. METHODS: National postal questionnaire survey of clinicians with potential responsibility for PDT provision. The survey explored reported local provision, beliefs about the effectiveness of PDT and what sources of opinion might influence attitudes towards providing PDT. RESULTS: The response rate was 73% (111/150). Almost half of the surveyed ophthalmology units routinely provided PDT, as part of a trend of steady growth in provision. The proportion of respondents who believed that further proof of effectiveness was required has also declined despite the absence of any new substantial evidence. Attitudes towards providing PDT were positive, on average, and were more strongly associated with perceived social pressure from local colleagues than from other sources. Local colleagues were seen as being most approving of PDT. CONCLUSION: Those responsible for implementing the NICE guidance need to address ophthalmologists' beliefs about the evidence of effectiveness for PDT and draw upon supportive local individuals or networks to enhance the credibility of the guidance.

Increasing use of a new health technology during the wait for NICE guidance: findings from the third national tracker survey of photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) is a relatively new treatment for neovascular age-related macular degeneration. Trial evidence suggests that repeated treatments with PDT can decrease the relative risk of a reduction in visual acuity over 2 years. Concerns raised over the clinical and cost effectiveness of the treatment prompted a technology appraisal by the National Institute for Clinical Effectiveness (NICE). Difficulties in assessing the possible benefit or otherwise of PDT have led to delays in the publication of guidance. During this time the introduction of PDT into the UK National Health Service (NHS) has continued. Over three annual tracker surveys, we describe trends in the provision of PDT in the NHS and potential difficulties in the implementation of NICE guidance. METHODS: We undertook surveys in each October of 2000, 2001 and 2002 of clinical directors or lead consultants in all NHS eye units. These sought data on which (if any) patients were referred or treated with PDT and the thresholds of support for the use of PDT. RESULTS: Response rates were 82 per cent, 79 per cent and 82 per cent. The proportion of units routinely providing PDT for patients with more than 50 per cent classic sub-foveal CNV increased from 8.5 per cent in 2000 to 31 per cent in 2002 (p <0.001). Units referring or treating no patients decreased from 35 per cent to 10 per cent between 2000 and 2002 (p <0.001). There was a significant fall in the proportion of units changing policies on provision between 2000-2001 and 2001-2002. The proportion of respondents requiring further evidence before supporting the use of PDT decreased from 33 per cent in 2000 to 20 per cent in 2002. CONCLUSION: There is evidence of a continuing growth in access to PDT in the absence of NICE guidance. Although 90 per cent of units offer some pathway to treatment important variations in reported provision remain. Given that PDT services are becoming established, there is a risk that clinical policy is determined by local service development as much as by national guidance.

Cost-effectiveness of photodynamic therapy for treatment of Barrett's esophagus with high grade dysplasia.

The purpose of this study was to compare the effectiveness and cost-effectiveness of photodynamic therapy (PDT) versus surgical esophagectomy and intensive endoscopic surveillance for patients with Barrett's esophagus and high-grade dysplasia (HGD) who are operative candidates. The results of our Markov Monte Carlo model show that PDT increased life expectancy by 1.8 years and quality-adjusted life expectancy (QALE) by 1.65 years when compared to the surveillance strategy. Relative to the esophagectomy strategy, PDT resulted in a greater life expectancy by 0.8 years and 2.17 additional quality-adjusted life years (QALYs). Although PDT cost 20,400 dollars and 7,100 dollars more than surveillance and esophagectomy respectively, the resulting incremental cost-effective ratios (ICERs) of 12,400 dollars/QALY and 3,300 dollars/QALY are within commonly accepted values. These findings were sensitive to the value assigned to the quality of life after PDT, but only at unrealistic values. In conclusion, PDT increases life expectancy and is cost-effective when compared to endoscopic surveillance and surgical esophagectomy.

A new health technology: where is the consensus on a clinically worthwhile benefit?

AIM: New therapies are often introduced into the NHS prior to full evaluation, leading to inequities in provision. Uncertainty exists regarding the value of photodynamic therapy in the treatment of neovascular age-related macular degeneration. We ascertained the availability of this treatment and the information used to inform clinical policy. METHODS: A postal survey of all clinical directors/lead consultants in the UK sought data on which (if any) patients were referred or treated with PDT by their unit, the sources of evidence informing clinical policy and the threshold of clinical benefit at which respondents would support the use of PDT. RESULTS: 123/152 questionnaires were returned. 42% of units make some provision for PDT on the NHS, including routine provision by 9%. 14.5% of units offer the option of care in the private sector, whilst 26.5% treated or referred no patients. The threshold at which respondents considered introduction of PDT would be justifiable varied widely. Respondents cited local literature review, advice from clinicians, guidance from the Royal College and information from the pharmaceutical industry as most influential in determining current policy. However, the National Institute for Clinical Excellence (NICE) and the Cochrane Library were anticipated as playing a greater role in shaping future practice. CONCLUSIONS: Substantial variation exists in the availability of PDT. Advocates of PDT may interpret our data as an indication of the NHS failing to provide an effective therapy equitably, whilst others may deduce that patients are receiving an under-evaluated treatment in routine clinical practice. The differing thresholds at which clinicians believe treatment would be justified may further exacerbate variations and the priority given to PDT.