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Background
The United States Food and Drug Administration (FDA) has approved the use of Laserscope's laser systems with QLT PhotoTherapeutics' light-activated porfimer sodium (Photofrin) for injection in treating early-stage, microinvasive lung cancer. In clinical studies of photodynamic therapy (PDT) for lung cancer, no candidates for PDT had metastatic lesions, nodal involvement or cancer recurrence, and surgery or irradiation was contraindicated because they had an underlying respiratory disease, such as emphysema.
The FDA also recently approved the use of light-activated porfimer sodium for relief of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial non-small cell lung cancer. Photodynamic therapy also shows promise as an alternative to esophageal resection for treatment for Barrett's esophagus, a pre-malignant lesion.
Photodynamic therapy has also been evaluated as an adjunct to stenting and drainage as a palliative treatment for unresectable bile duct cancer. Small randomized controlled trials (RCTs) have demonstrated improvements in survival, and the results of a phase III study sponsored by the National Cancer Institute is pending publication. Zoepf et al (2005) conducted a RCT (phase IIb) of PDT in persons with advanced bile duct cancer. A total of 32 patients with non-resectable cholangiocarcinoma were randomized. Light activation was performed in the patients assigned to PDT 48 hours after intravenous application of 2 mg/kg body weight of Photosan-3, an oligomer of hematoporphyrin that has been approved for use in the European Union but is not approved by the FDA. In the control group, patients were treated with stenting and drainage without PDT. The investigators stated that the PDT group and the control group were comparable due to age, gender, performance status, bilirubin level, and bile duct cancer stage. The investigators reported that the median survival time after randomization was 7 months for the control group and 21 months for the PDT group (p = 0.0109). The investigators noted that, in 50 % of the initially percutaneously treated patients, they were able to change from percutaneous to transpapillary drainage after PDT. The investigators noted that PDT was associated with a considerable rate of cholangitis: 4 patients showed infectious complications after PDT versus 1 patient in the control group.
Ortner et al (2003) reported on a prospective, open-label, randomized study with a group sequential design comparing PDT plus stenting (n = 20) to stenting alone (n = 19) in patients with non-resectable cholangiocarcinoma. For PDT, 2 mg/kg porfimer sodium (Photofrin) was injected intravenously 2 days before intraluminal photoactivation. Further treatments were performed in cases of residual tumor in the bile duct. The investigators reported that PDT resulted in prolongation of survival, with median survival of 493 days in persons assigned to PDT plus stenting, compared to a median survival of 98 days in persons assigned to stenting alone (p < 0.0001). The investigators noted that PDT also improved biliary drainage and quality of life. The investigators noted that this study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical.
Photodynamic therapy for tumors other than obstructing esophageal cancer, inoperable cholangiocarcinoma, and endobronchial non-small cell lung cancer is considered investigational, because it has not been proven to improve the survival of patients with other tumors. Photodynamic therapy is being investigated as a treatment for cancers of the breast and brain.
Photodynamic therapy has been extensively studied for the treatment of various superficial non-melanoma skin cancers. For PDT for superficial skin cancers, a photosensitizing porphyrin (5-aminolevulinic acid, methyl aminolevulinate) is generally applied topically to the lesion. Although a porphyrin (porfimer sodium, Photofrin) can be administered systemically, this approach is avoided since systemic for treatment of skin cancers as such therapy can be associated with prolonged photosensitivity.
A recently published study found that PDT had good cosmetic results, but had a significantly higher recurrence rates than excision. Rhodes et al (2007) reported on the results of a prospective, multi-center, randomized study where 97 patients with 105 non-pigmented nodular basal cell carcinomas (BCCs) were treated with 2 to 4 courses of methyl aminolevulinate (MAL) PDT or with excision using 5-mm margins. The patients were followed for 5 years. The raw 5-year recurrence rate among successfully treated MAL-PDT patients was 14 %, significantly higher than the 4 % recurrence rate among excision patients. When initial treatment failures were included, the 5-year cure rates dropped to 66.0 % in the MAL-PDT group and to 91.5 % in the excision group. The overall cosmetic outcome at 5 years was rated as good or excellent in 87 % of the MAL-PDT patients, which was significantly better than the 54 % rated as good or excellent in the surgery patients.
In a prospective, multi-center, non-comparative study, Vinviullo et al (2005) examined the safety and effectiveness of PDT using topical MAL for basal cell carcinoma (BCC) defined as "difficult to treat", i.e., large lesions, in the H-zone (located in the mid-face), or in patients at high-risk of surgical complications. Patients were assessed 3, 12 and 24 months after the last PDT treatment. A total of 102 patients with "difficult-to-treat" BCC were treated with MAL PDT, using 160 mg g(-1) cream and 75 J cm(-2) red light (570 to 670 nm), after lesion preparation and 3 hours of cream exposure. A total of 95 patients with 148 lesions were included in the final analysis. The histologically confirmed lesion complete response rate at 3 months was 89 % (131 of 148). At 12 months, 10 lesions had re-appeared, and therefore the cumulative treatment failure rate was 18 % (27 of 148). At 24 months, an additional 9 lesions had re-appeared, resulting in a cumulative treatment failure rate of 24 % (36 of 148). The estimated sustained lesion complete response rate (assessed using a time-to-event approach) was 90 % at 3 months, 84 % at 12 months and 78 % at 24 months. Overall cosmetic outcome was judged as excellent or good in 79 % and 84 % of the patients at 12 and 24 months, respectively. Follow-up is continuing for up to 5 years. These investigators concluded that PDT by means of MAL is an attractive option for "difficult-to-treat" BCC.
Other photosensitizers are under investigation for skin cancers. In a clinical trial, Kaviani et al (2005) examined the use of PDT for the treatment of various pathological types of BCC. Six patients with 30 lesions underwent PDT. The photosensitizer used was Photoheme, a hematoporphyrin derivative IX. It was injected intravenously at the dose of 2 to 3.25 mg/kg. After 24 hours, the lesions were illuminated by laser light (lambda = 632 nm, light exposure dose = 100-200 J/cm2). Lesions were evaluated pre- and post-operatively and at follow-up sessions (of up to 6 months). After a single session of PDT, the average response rate in different histopathological types of BCC (e.g., ulcerative, superficial, nodular, and pigmented forms) were 100 %, 62 %, 90 %, and 14 %, respectively. In patients who responded completely, the cosmetic results were excellent and there were no recurrence at 6th month of follow-up. These researchers concluded that although PDT seems to be an effective treatment modality for superficial, ulcerative, and nodular BCC, it is not recommended for pigmented lesions.
In a phase I clinical trial, Chan et al (2005) examined the pharmacokinetic properties of Npe6 and clinical response to PDT with this photosensitizer. A single intravenous dose of Npe6 was administered to 14 cancer patients with superficial malignancies (BCC = 22 lesions, squamous cell cancer = 13 lesions, papillary carcinoma = 14 lesions). Patients received one of five ascending doses (0.5 mg/kg (n = 4), 1.0 mg/kg (n = 3), 1.65 mg/kg (n = 3), 2.5 mg/kg (n = 3), or 3.5 mg/kg (n = 1)) 4 to 8 hours prior to light activation. The total light dose (range 25 to 200 J/cm2) depended on the tumor shape and size. Light was delivered using an argon-pumped tunable dye laser. Serum NPe6 concentrations were measured over a 28-day period. The toxicity and cutaneous clinical efficacy of NPe6 were observed. Four weeks after PDT, 20 of 22 BCC tumors (91 %) showed a complete response; 18 of 27 other malignant cutaneous tumors showed a complete (n = 15/27, 56 %) or partial (n = 3/27, 11 %) response. Fewer non-responders were seen at an Npe6 dose level of 1.65 mg/kg or higher. Only 2 of 14 patients experienced an adverse event that was definitely related to NPe6 administration. Photosensitivity resolved within 1 week of NPe6 dosing in 12 of 14 patients. Analysis of serum levels of 11 patients indicated that a 2-compartment model with a residual phase best fits the data. The mean alpha, beta, and terminal half-lives were 8.63 +/- 2.92, 105.90 +/- 37.59 and 168.11 +/- 53.40 hours (+/- 1 SD), respectively. The observed mean volume of distribution was 5.94 +/- 2.55 liters, and the mean clearance was 0.0394+/-0.0132 liters/hour. These values were independent of the dose administered. The authors concluded that the photosensitizer, NPe6, was well-tolerated with minimal phototoxic side effects, and demonstrated preliminary effectiveness against cutaneous malignancies.
In a review on photodynamic therapy for non-melanoma skin cancer, Szeimies et al (2005) stated that PDT is a treatment modality that has been shown to be effective mainly for the dermato-oncological conditions such as actinic keratoses, cutaneous lesions of Bowen's disease, in situ squamous cell carcinoma, and BCC. This is in agreement with the observations of Babilas et al (2005). Garcia-Zuazaga et al (2005) noted that PDT has been approved by the FDA to treat actinic keratoses. In Europe, PDT is currently being used in the treatment of actinic keratoses and BCC. Other off-label uses of PDT include cutaneous lesions of Bowen's disease, and cutaneous T-cell lymphoma. The Finnish Medical Society’s guideline on skin cancer (2005) included PDT a treatment option for basilomas (e.g., BCC).
The National Institute for Health and Clinical Excellence (NICE, 2006) guideline on PDT for non-melanoma skin tumors (including pre-malignant and primary non-metastatic skin lesions) stated that “evidence of efficacy of this procedure for the treatment of basal cell carcinoma, Bowen’s disease and actinic (solar) keratoses is adequate to support its use for these conditions …. Evidence is limited on the efficacy of this procedure for the treatment of invasive squamous cell carcinoma”. The specialist Advisors of this report noted that PDT is appropriate for large superficial lesions of Bowen’s disease, actinic keratoses, and BCC, especially where there are multiple lesions and where repair would otherwise require extensive surgery. This report also stated that a Cochrane review is being developed on PDT for localized squamous cell carcinoma of the skin and its precursors.
The National Comprehensive Cancer Network has recently added MAL as an example of PDT that can be used in patients with low-risk, superficial basal cell skin cancer, where surgery or radiation is contraindicated or impractical.
Du et al (2006) stated that interstitial PDT is an emerging modality for the treatment of solid organ disease. These investigators have performed extensive research that showed the feasibility of interstitial PDT for prostate cancer. This study reported their pre-clinical and clinical experience in this therapeutic approach. These researchers have treated 16 dogs in pre-clinical studies, as well as 16 human subjects in a phase I study, using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light fluence, drug level and oxygen distribution for these patients were performed. They reported the safe and comprehensive treatment of the prostate using PDT. However, there was significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate. The authors concluded that PDT is an attractive option for the treatment of prostate adenocarcinoma. However, the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility. Their future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time, in order to deliver a consistent overall PDT dose distribution.
In a review on the use of focal therapy for localized prostate cancer, Eggener and co-workers (2007) stated that several emerging technologies (e.g., high-intensity focused ultrasound, cryotherapy, radiofrequency ablation, and PDT) seem capable of focal destruction of prostate tissue with minimal morbidity. These researchers encouraged the investigation of focal therapy in select men with low-risk prostate cancer in prospective clinical trials that carefully document safety, functional outcomes and cancer control.
Moore et al (2009) noted that debate is ongoing about the treatment of organ-confined prostate cancer, particularly in men who have low-risk disease detected by PSA screening. A balance is needed between the harms and benefits of treatment. New techniques are being developed that aim to offer similar treatment effects to current radical therapies, while reducing the associated harmful effects of these treatments. These researchers explored the potential of PDT for the treatment of organ-confined prostate cancer. They stated that clinical studies are underway to investigate the use of PDT for primary and salvage treatment of organ-confined prostate cancer.
Recurrent respiratory papillomatosis (RRP), which is caused by human papillomavirus (HPV) types 6 and 11, is the most common benign neoplasm of the larynx among children and the second most frequent cause of childhood hoarseness. After changes in voice, stridor is the second most common symptom, first inspiratory and then biphasic. Less common presenting symptoms include chronic cough, recurrent pneumonia, failure to thrive, dyspnea, dysphagia, or acute respiratory distress, especially in infants with an upper respiratory tract infection. Differential diagnoses include asthma, croup, allergies, vocal nodules, or bronchitis. Reports estimate the incidence of RRP in the United States at 4.3 per 100,000 children and 1.8 per 100,000 adults. Infection in children has been associated with vertical transmission during vaginal delivery from an infected mother. Younger age at diagnosis is associated with more aggressive disease and the need for more frequent surgical procedures to decrease the airway burden. When surgical therapy is needed more frequently than 4 times in 12 months or there is evidence of RRP outside the larynx, adjuvant medical therapy should be considered. Adjuvant therapies that have been investigated include dietary supplements, control of extra-esophageal reflux disease, potent anti-viral and chemotherapeutic agents, and PDT; although several have shown promise, none to date has "cured" RRP, and some may have serious side effects (Derkay and Wiatrak, 2008).
In a parallel-arm, randomized study, Shikowitz and colleagues (2005) examined the effectiveness of PDT with meso-tetra (hydroxyphenyl) chlorin (m-THPC) photosensitizer for RRP. Disease extent was scored and papillomas were removed during direct endoscopy every 3 months after enrollment. Of 23 patients aged 4 to 60 years enrolled in the study, 15 patients, plus 2 in the late group without PDT owing to airway risk, completed the study. Six patients withdrew voluntarily after PDT. Subjects received intravenous administration of m-THPC 6 days before direct endoscopic PDT (80 to 100 J of light for adults and 60 to 80 J for children). Main outcome measures were difference in severity scores between the early and late groups and between pre- and post-PDT scores for all patients. Secondary measures were the associations between baseline characteristics and response and changes in immune response and the prevalence of latent viral DNA. There were significant differences between groups, with marked improvement in laryngeal disease across time after PDT (p = 0.006). Five of 15 patients were in remission 12 to 15 months after treatment, but there was recurrence of disease after 3 to 5 years. Tracheal disease was not responsive to PDT. No change occurred in the prevalence of latent human papillomavirus DNA. The immune response to virus improved with clinical response. The authors concluded that the use of m-THPC PDT reduces the severity of laryngeal papillomas, possibly through an improved immune response. However, failure to maintain remission with time suggested that this is not an optimal treatment.
Goon et al (2008) stated that HPV infection in benign laryngeal papillomas is well- established. The vast majority of RRP lesions are due to HPV types 6 and 11. Human papillomaviruses are small non-enveloped viruses (greater than 8 kb), that replicate within the nuclei of infected host cells. Infected host basal cell keratinocytes and papillomas arise from the disordered proliferation of these differentiating keratinocytes. Surgical debulking of papillomas is currently the treatment of choice; newer surgical approaches utilizing microdebriders are replacing laser ablation. Surgery aims to secure an adequate airway and improve and maintain an acceptable quality of voice. Adjuvant treatments currently used include cidofovir, indole-3-carbinol, ribavirin, mumps vaccine, and PDT. The recent licensing of prophylactic HPV vaccines is a most interesting development. The low incidence of RRP does pose significant problems in recruitment of sufficient numbers to show statistical significance. The authors noted that large multi-center collaborative clinical trials are therefore needed.
Sebaceous hyperplasia (SH) is a common benign skin condition involving hypertrophy of sebaceous glands. Lesions occur particularly on the central face of adults. Patients usually are concerned about the lesions either because of fear of skin cancer or because of cosmesis. There is some evidence to suggest that chronic immunosuppression, such as from transplantation, can lead to the development of this condition. Treatment with electrodessication or laser ablation is successful; oral isotretinoin has been used in patients with multiple lesions. On the other hand, there is only limited evidence for the effectiveness of treatment with topical 5-aminolevulinic acid (Levulan Kerastick).
Richey (2007) stated that current therapies for SH have a high-risk for adverse effects and recurrence of treated lesions. The theoretic basis for the treatment of SH by PDT with 5-aminolevulinic acid (ALA) has been established. Studies show that 1 hour is sufficient ALA incubation time to achieve clearance, and ALA-induced protoporphyrin IX may be activated with a 585-nm pulsed dye laser device, blue light source, or an intense pulsed light device. Complete clearance may be achieved with 1 to 6 treatments; however, long-term recurrence rates are not established.
Wang and colleagues (2007) carried out a prospective, single-arm, phase II study of 5-ALA-PDT in the treatment of recalcitrant viral warts in an Asian population. Recalcitrant viral warts were surgically pared, and then treated with 20 % 5-ALA cream under occlusion for 4 hrs before irradiation with a red light source (Waldmann PDT1200; wavelength, 590 to 700 nm) at an irradiance of 50 mW/cm(2) and a total dose of 50 J/cm(2). Photodynamic therapy was repeated fortnightly for a maximum of 4 times. A total of 12 adult Asian patients were enrolled into the study (10 males, 2 females). The mean age of the patients was 32.8 years (range of 18 to 70). They had skin phototypes III-IV. Nine patients had plantar warts and 3 patients had hand warts (2 had warts on the fingers, 1 had a wart on the palm). Five patients (42 %) showed complete disappearance of their warts, 1 patient (8 %) showed partial clearance (greater than 50 % decrease in the wart area), 5 patients (42 %) had stable disease (less than 50 % decrease in the wart area), and 1 (8 %) showed progressive disease (increase in the wart area). Adverse effects included mild-to-moderate pain and erythema, which lasted no longer than 48 hrs and was well-tolerated by all patients. None of the patients withdrew from the study because of side-effects. The authors concluded that 5-ALA-PDT, given its non-invasiveness, minimal adverse effects, and good cosmetic results, is a promising alternative treatment for recalcitrant viral warts. They stated that further studies with a larger cohort of patients would be of value.
Hidradenitis suppurative (HS) is a chronic, apocrine, dermatological disorder that has a genetic predisposition. Rose and Stables (2008) reviewed the evidence on the use of PDT in the treatment of HS. Although small in number, there is considerable variation in the application of topical photosensitisers, light sources used and treatment regimes. In addition, there is often limited information about patient selection in terms of disease severity and measuring precise patient outcome. The authors stated that these issues need to be addressed in future studies in order to accurately determine the role of PDT in HS.
Hamiton et al (2009) performed a systematic review of randomized controlled trials of light and laser therapies for acne vulgaris. These investigators searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycInfo, LILACS, ISI Science Citation Index and Dissertation Abstracts International for relevant published trials. They identified 25 trials (694 patients), 13 of light therapy and 12 of light therapy plus light-activated topical cream (PDT). Overall, the results from trials of light alone were disappointing, but the trials of blue light, blue-red light and infrared radiation were more successful, particularly those using multiple treatments. Red-blue light was more effective than topical 5 % benzoyl peroxide cream in the short-term. Most trials of PDT showed some benefit, which was greater with multiple treatments, and better for non-inflammatory acne lesions. However, the improvements in inflammatory acne lesions were not better than with topical 1 % adapalene gel, and the side-effects of therapy were unacceptable to many participants. The authors concluded that some forms of light therapy were of short-term benefit. Patients may find it easier to comply with these treatments, despite the initial discomfort, because of their short duration. However, very few trials comparing light therapy with conventional acne treatments were conducted in patients with severe acne or examined long-term benefits of treatment.
Reporting on the results of a case series (n = 3), Nayeemuddin and colleagues (2002) concluded that "[t]he results obtained in this small case series suggest that topical PDT is not a promising treatment for disseminated superficial actinic porokeratosis".
Exadaktylou et al (2003) evaluated the effectiveness of PDT in selected patients with Darier's disease (keratosis follicularis). A total of 6 patients with Darier's disease were assessed before and after treatment with PDT using 5-ALA and mean fluence rates of 110-150 mW cm-2. Of the 6 patients, 1 was unable to tolerate the treatment. Of the remaining 5, all experienced an initial inflammatory response that lasted 2 to 3 weeks. In 4 of the 5 patients, this was followed by sustained clearance or improvement over a follow-up period of 6 months to 3 years. Three of these 4 patients were on systemic retinoids and the 4th had discontinued acitretin prior to PDT. In the 5th patient partial improvement was followed by recurrence after etretinate therapy was discontinued. Biopsy specimens taken immediately after the procedure in 2 patients demonstrated a mild inflammatory cell infiltrate in the dermis. A biopsy obtained 18 months after PDT from a successfully treated area showed no signs of Darier's disease and a subtle increase of collagen in the upper dermis. The authors concluded that PDT can be viewed as a potential adjunctive modality for Darier's disease but should not be considered as a substitute for retinoids in patients who require systemic treatment.
Bryld and Jemec (2007) assessed the possible benefit of PDT in the treatment of rosacea. An exploratory review of case notes from rosacea patients treated with PDT was performed. Patients referred to the authors' department with rosacea were offered PDT if requesting an alternative to previously tried conventional therapy. Routine MAL-PDT with methylamino levulate and red light was given 1 to 4 times; results were evaluated 1 to 2 months after PDT was initiated and subsequently followed-up. Good results were seen in 10 out of 17 patients, and fair results in another 4 patients. The majority of patients treated could stop or significantly reduce other rosacea therapy for a period lasting from about 3 months and up to 2 years. The study was limited by strong selection bias, and the clinical evaluation was obtained from case notes and photos. The authors concluded that an apparent effect of MAL-PDT on rosacea could be observed. This is in accordance with their previous experience, and observations made by other researchers. Thus, they stated that a future randomized controlled trial seems justifiable.
In a systematic review and meta-analysis, Azarpazhooh et al (2010) evaluated the effectiveness of PDT for periodontitis in adults as a primary mode of treatment or as an adjunct to non-surgical treatment of scaling and root planing (SRP) compared to a conventional non-surgical SRP treatment. MEDLINE, EMBASE, CINAHL, other relevant databases, and the International Pharmaceutical Abstracts were searched from their inception until May 2009 for randomized controlled trials of PDT compared to a placebo, no intervention, or non-surgical treatment in an adult population. Data on changes in clinical attachment level (CAL), probing depth, gingival recession, and full-mouth plaque or bleeding scores were extracted and meta-analyzed, and the pooled mean difference (MD) was reported. A total of 5 studies were included in this review. These studies had a small sample size for some of the performed analysis with a moderate to high risk of biases. There were clinical heterogeneities among included studies. Photodynamic therapy as an independent treatment or as an adjunct to SRP versus a control group of SRP did not demonstrate statistically or clinically significant advantages. Combined therapy of PDT + SRP indicated a probable efficacy in CAL gain (MD: 0.34; 95 % confidence interval [CI]: 0.05 to 0.63) or probing depth reduction (MD: 0.25 mm; 95 % CI: 0.04 to 0.45 mm). The authors concluded that PDT as an independent treatment or as an adjunct to SRP was not superior to control treatment of SRP. Thus, the routine use of PDT for clinical management of periodontitis can not be recommended. They stated that well-designed clinical trials are needed for proper evaluation of this therapy.
Nekam's disease, also known as keratosis lichenoides chronica (KLC), is a rare dermatosis characterized by violaceous papular and nodular lesions, often arranged in a linear or reticulate pattern on the dorsal hands and feet, extremities, and buttock. Lopez-Navarro et al (2008) stated that KLC is a rare, acquired disorder of keratinization of unknown etiology. The disease has a chronic and progressive course and is characterized by a poor response to almost all topical treatments and most systemic regimens. These investigators reported the first case of KLC in which there was a marked response in localized areas to PDT with methyl 5-ALA. The findings of this case study need to be validated by well-designed studies.
Radiation retinopathy (RR) is a chronic and progressive condition that results from exposure to any source of radiation. It might be secondary to radiation treatment of intra-ocular tumors such as choroidal melanomas, retinoblastomas, and choroidal metastasis, or from unavoidable exposure to excessive radiation from the treatment of extra-ocular tumors like cephalic, nasopharyngeal, orbital, and para-nasal malignancies. Giuliari et al (2011) reviewed the currently available therapeutic modalities for RR, including newer investigational interventions directed towards specific aspects of the pathophysiology of this refractory complication. A review of the literature encompassing the pathogenesis of RR and the current therapeutic modalities available was performed. After the results of the Collaborative Ocular Melanoma Study, most of the choroidal melanomas were being treated with plaque brachytherapy increasing by that the incidence of this radiation complication. Radiation retinopathy has been reported to occur in as many as 60 % of eyes treated with plaque radiation, with higher rates associated with larger tumors. Initially, the condition manifests as a radiation vasculopathy clinically seen as microaneurysms and telangiectases, with posterior development of retinal hard exudates and hemorrhages, macular edema, neovascularization and tractional retinal detachment. Photodynamic therapy, laser photocoagulation, oral pentoxyphylline and hyperbaric oxygen have been attempted as treatment modalities with inconclusive results. Intravitreal injections of anti-vascular endothelial growth factor (e.g., bevacizumab, ranibizumab and pegaptanib sodium) have been recently used, also with variable results. The authors concluded that RR is a common vision threatening complication following radiation therapy. The available therapeutic options are limited and show unsatisfactory results. They stated that further large investigative studies are needed for developing better therapeutic as well as preventive treatment strategies.
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