Ocular Photodynamic Therapy Research Articles

An Asymptomatic Circumscribed Choroidal Hemangioma: A Case Report

This paper reviews the clinical characteristics of a circumscribed choroidal hemangioma (CCH). This rare, benign ocular tumor often goes undiagnosed until it causes secondary complications such as macular edema. It is critical to differentiate a CCH from malignant posterior segment tumors such as choroidal melanoma. Ocular photodynamic therapy is an important treatment option for patients with symptomatic CCH. CE Notification: This article is available as a COPE accredited CE course. You may take this course for 1-hour credit. Read the article and take the qualifying test to earn your credit. Click here to Enroll (https://www.crojournal.com/an-asymptomatic-circumscribed-choroidal-hemangioma-a-case-report) Please check COPE course expiry date prior to enrollment. The COPE course test must be taken before the course expiry date.

Clinical Efficacy and Safety of Current Interventions for Choroidal Neovascularization Associated with Rare Diseases: A Systematic Literature Review.

The aim of this systematic literature review was to evaluate the efficacy and safety of interventions for the treatment of choroidal neovascularization (CNV) secondary to etiologies other than age-related macular degeneration and pathologic myopia. Relevant randomized controlled trials (RCTs) and prospective observational studies were identified by searching MEDLINE, MEDLINE In-Process, EMBASE, and CENTRAL. The search identified 5 RCTs; no relevant observational studies were identified. The studies differed in terms of underlying cause of CNV, patient numbers (n = 9-178), follow-up time (2-36months) and quality assessment. In the largest RCT (n = 178 across a range of rare CNV etiologies), intravitreal ranibizumab showed superior efficacy versus sham from baseline to month 2 [mean best-corrected visual acuity (BCVA): + 9.5 vs. - 0.4 letters; p < 0.001]; the gain was maintained up to month 12. In the treatment of CNV secondary to presumed ocular histoplasmosis syndrome (POHS), both intravitreal ranibizumab and photodynamic therapy (PDT) showed significant improvement from baseline BCVA over the 12-month period (n = 9); however, all patients in the PDT group required rescue ranibizumab therapy. Unlicensed intravitreal bevacizumab was associated with a statistically significant improvement in BCVA compared to PDT at 12months (p < 0.001) in patients with CNV secondary to multifocal choroiditis (n = 27). The use of steroids before PDT showed better BCVA outcomes than PDT alone (p < 0.05) in patients with idiopathic CNV (n = 20). Argon green laser therapy showed limited efficacy in patients with CNV secondary to OHS (n = 134). There is evidence from a relatively large, good-quality study to support the use of intravitreal ranibizumab for the treatment of CNV secondary to rare diseases. However, the limited number of RCTs for this indication and differences in study characteristics between RCTs mean that there is uncertainty regarding comparative clinical effectiveness of interventions. RCTs with an active comparator are required to fully establish the comparative effectiveness of treatments for CNV secondary to rare diseases. Novartis Pharmaceuticals UK Ltd, Surrey, UK.

Failure of ocular photodynamic therapy for secondary choroidal metastasis: a case report and literature review.

The choroid is the most common site for intraocular metastatic disease. Photodynamic therapy (PDT) can effectively destroy malignant tissue and induce anti-tumor activity. Recent publications support its use as an effective therapy for the treatment of choroidal metastases, especially in the subfoveal region, resulting in subsequent vision preservation or improvement. Here, we introduce a case of choroidal metastasis, secondary to primary lung cancer. The progression of choroidal metastasis after PDT was followed up using spectral domain optical coherence tomography with point-to-point follow-up. Unfortunately, both the choroidal metastasis and serous retinal detachment increased after PDT. Since the mechanism underlying the therapeutic effect of PDT on choroidal metastasis is still not fully understood, deeper investigations into its safety, underlying molecular mechanisms, and treatment effects are critical for further PDT clinical usage in intraocular choroidal metastases.

Hypocrellin B and nano silver loaded polymeric nanoparticles: Enhanced generation of singlet oxygen for improved photodynamic therapy

A nanoparticulate photodynamic approach was employed with an objective to achieve enhanced production of singlet oxygen (1O2), for the management of posterior segment eye diseases like age related macular degeneration. The hypocrellin B (HB) loaded poly lactide-co-glycolide nanoparticle formulations were incorporated with nano silver (HBS-NPs). The optimized HBS-NPs contained 2.60±0.06mg/mL of HB and showed (i) 135.6 to 828.2nm size range, and (ii) negative zeta potential with a narrow polydispersity index. The DSC thermograms suggested the amorphous nature of HB inside the HBS-NPs. With the average encapsulation efficiency of 92.9±1.79%, the drug release from the HBS-NPs followed a biphasic pattern with an initial burst of 3.50% during first 8h followed by a sustained release of 47.82% within 3days. The interaction between nano silver and HB as assessed by the increase in spectral intensity of Raman spectrum demonstrates that HB may be attached over the nano silver. Generation of reactive oxygen species (ROS) by HBS-NPs was significantly higher than that of HB/HB-NPs. The singlet oxygen generating efficiency assessed using EPR spectrometer follows the order of nano silver>HB-NPs>pure HB drug solution>HBS-NPs. The HBS-NPs had a concentration and time dependent phototoxicity on A549 (human adeno lung carcinoma) cells in the presence of light providing a superior phototoxic effect (82.2% at 50μM) at 2h irradiation. The CAM treated with HBS-NPs showed a significant anti-angiogenic effect compared to a blank formulation. In vivo biodistribution studies revealed that intravenous administration of HBS-NPs lead into significant exposure to the posterior segment of the eye. This proof of principle study demonstrates that HB based nanoparticles may be a valuable new tool for application in ocular photodynamic therapy for the treatment of AMD in future.

Photodynamic Therapy for Conjunctival Ocular Surface Squamous Neoplasia

To report the case about a patient with conjunctival ocular surface squamous neoplasia who responded well to ocular photodynamic therapy (PDT). A 75-year-old man underwent PDT for his biopsy-proven conjunctival squamous cell dysplasia that was extending onto the cornea. Patient received 2 treatments of PDT with verteporfin (6 mg/m(2) body surface area, intravenously) with 2 months apart. The light dose was calculated as 50 J/cm(2). Whole lesion was irradiated 1 min after injection. Half of the mass regressed after first PDT. Second PDT resulted in near-complete cure of remaining lesion within 2 weeks. The patient remained stable for the 13 months. PDT may be useful in some cases of extensive ocular surface squamous neoplasia that is less than invasive.

Color Doppler Imaging of Ocular Blood Flow after Combined Photodynamic Therapy with Intravitreal Triamcinolone in Age-Related Macular Degeneration

Purpose: To investigate the effect of combined intravitreal triamcinolone and ocular photodynamic therapy on retinal and choroidal hemodynamics in age-related macular degeneration.Methods: Intravitreal triamcinolone (4 mg, 0.1 cc) and photodynamic therapy with verteporfin were applied to 48 eyes of 33 subjects (25 male and 8 female; mean age: 68.9 years) with subfoveal choroidal neovascular membrane secondary to age-related macular degeneration. Patients were assessed for ocular hemodynamic parameters with color Doppler imaging 24 hr before and 1 week, 1 month, and 3 months after a single-dose administration of combined intravitreal triamcinolone and photodynamic therapy.Results: Throughout the study period, no significant difference in resistance index, peak systolic velocity, or end diastolic velocity existed in the ophthalmic artery (P = 0.58, P = 0.18, and P = 0.19, respectively), the posterior ciliary arteries (P = 0.73, P = 0.19, and P = 0.34, respectively), or the central retinal artery (P = 0.09, P = 0.32, and P = 0.47, respectively).Conclusion: Combined intravitreal triamcinolone and photodynamic therapy was not associated with any alteration in ocular blood flow or flow velocity over 3 months in eyes with age-related macular degeneration.

Current indications for ocular photodynamic therapy – A review of the literature and two case reports

Abstract Background Presentation of the current treatment indications for photodynamic therapy (PDT) with verteporfin in the management of different choroidal diseases. Methods A review is given of the standard treatment protocol, the results of published clinical trials and cohort or case-control studies with two clinical examples. Results Monotherapy with PDT for neovascular age-related macular degeneration is no longer a first-line therapy. The reasoning behind combining PDT with an antiangiogenic treatment with anti-vascular endothelial growth factor is to decrease the number of re-treatments. In other diseases of the choroid, such as circumscribed choroidal hemangioma or central serous chorioretinopathy, use of PDT with verteporfin as a monotherapy may prove to be an effective method to improve or stabilize vision in the majority of patients. Conclusions Verteporfin PDT still represents an effective and safe treatment because of its selectivity to the choroid.

Photodynamic Therapy for Iatrogenic CNV Due to Laser Photocoagulation in Central Serous Chorioretinopathy

The authors report the result of photodynamic therapy for iatrogenic choroidal neovascularization from focal argon laser photocoagulation in a case with central serous chorioretinopathy. A 45-year-old woman who developed choroidal neovascularization after focal argon laser photocoagulation for chronic central serous chorioretinopathy was treated with ocular photodynamic therapy with verteporfin. Choroidal neovascularization became inactive clinically a month after photodynamic therapy. Fluorescein angiography and optical coherence tomography demonstrated the resolved choroidal neovascularization. Baseline visual acuity improved from 20/40 to 20/20 after photodynamic therapy. The patient's condition remained stable 2 years postoperatively. Photodynamic therapy was beneficial for the outcome of iatrogenic choroidal neovascularization that developed after laser treatment for longstanding central serous chorioretinopathy.

Treatment of neovascular age-related macular degeneration: past, present and future directions

The treatment options of choroidal neovascularization due to age-related macular degeneration have expanded. Prior to ocular photodynamic therapy the only available treatment was laser photocoagulation. Clinicians and patients were not particularly enthusiastic despite its ability to stabilize vision. The purpose of the review is to review the past and current concepts of neovascular age-related macular degeneration therapy and to provide a short overview of upcoming treatments. Photodynamic therapy provided us with the first realistic means to address subfoveal choroidal neovascularization lesions from age-related macular degeneration. Antivascular endothelial growth factors now allow better visual outcomes than mere stabilization of vision and other promising treatments are undergoing study at this time. Age-related macular degeneration therapy has undergone a significant revolution in recent years. Understanding the historical perspective of treatment provides a better appreciation of current therapies. Still there is no cure for this disease and more promising treatments are currently under investigation.

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

Photodynamic therapy of subfoveal neovascular membrane in type 2A idiopathic juxtafoveolar retinal telangiectasis

Purpose To evaluate the effect of photodynamic therapy on subfoveal neovascular membrane related to type 2A idiopathic juxtafoveolar retinal telangiectasia. Design Interventional case series. Methods Retrospective review of four eyes of four patients who underwent photodynamic therapy for subfoveal neovascular membrane secondary to idiopathic juxtafoveolar retinal telangiectasia. Ocular photodynamic therapy with verteporfin was performed in all cases using standard protocols. Results are given in terms of final visual acuity and neovascular membrane activity based on clinical examination, fluorescein and indocyanin green angiography, and, in two cases, optical coherence tomography. Results Baseline visual acuity of 20/30 and 20/40 (×2) was maintained in three patients after one, two, and three sessions of photodynamic therapy respectively, and a follow-up of 23, 21, and 9 months. Leakage specific to the subfoveal neovascular membrane ceased on the fluorescein angiography. In the other patient, the final vision decreased from 20/50 to 20/200 after four sessions of photodynamic therapy and a follow-up of 14 months. Although there was still mild persistent leakage on the fluorescein angiography, neovascular membrane size was unchanged, and no subretinal fluid was demonstrated on optical coherence tomography. Conclusions Data from this case series suggest that photodynamic therapy may be effective in managing subfoveal neovascular membrane associated with idiopathic juxtafoveolar retinal telangiectasia, which usually carries a poor visual prognosis. Prospective study is required to confirm the beneficial effect of this treatment.

Record spending for British pharmaceutical R&amp;D in 2003

Record spending for British pharmaceutical R&amp;D in 2003

Ocular Photodynamic Therapy in Choroidal Neovascularization Complicating Idiopathic Central Serous Chorioretinopathy

Two consecutive patients with idiopathic central serous chorioretinopathy and decreased vision subsequent to subfoveal choroidal neovascular membranes were treated with photodynamic therapy applied using the protocol of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study Group. Main outcome measures included best-corrected visual acuity, biomicroscopic appearance, and leakage on fluorescein and indocyanine green angiography. Photodynamic therapy offered anatomical, angiographic, and functional improvement. After an initial complete response, the patients required re-treatment at 3 and 4 months, respectively. Cessation of leakage with improvement in visual acuity occurred, but subretinal fibrosis posed a possible limitation for full functional recovery. Although choroidal neovascular membranes complicating idiopathic central serous chorioretinopathy portend a poor visual prognosis, the overall response to photodynamic therapy was favorable.

Verteporfin ocular photodynamic therapy

This article reviews the pharmacotherapeutics of verteporfin (Visudyne®, Novartis Pharma AG) used in ocular photodynamic therapy. The chemistry, pharmacokinetics and pharmacodynamics of the drug are reviewed. The article highlights and summarises the results of the multi-centre, randomised, controlled clinical trials with verteporfin to treat subfoveal choroidal neovascularisation in age-related macular degeneration, ocular histoplasmosis syndrome and pathologic myopia. In addition, the safety profile and side effects of verteporfin are discussed.

Macular translocation surgery with 360-degree peripheral retinectomy following ocular photodynamic therapy of choroidal neovascularization

Purpose To determine the visual outcomes of eyes that underwent macular translocation surgery with 360 degrees peripheral retinectomy and silicone oil tamponade (MTS360) following ocular photodynamic therapy (OPT) with verteporfin for subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration (ARMD). Design Observational case series. Methods A retrospective review of patients who underwent MTS360 with silicone oil tamponade from August 5, 1998 through December 1, 2002. Patients who had at least one episode of OPT with verteporfin before surgery were identified. The number of OPT session, best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, complications (including postoperative CNV, retinal detachment [RD]), the presence or absence of cystoid macular edema (CME) by optical coherence tomography (OCT) were recorded. Results Eight eyes of eight patients were identified that fulfilled the inclusion criteria. All eyes had at least one episode of OPT (mean, 1.5 treatments). All of these patients at the time of MTS360 demonstrated continued visual loss following the most recent OPT session. The mean preoperative visual acuity was 56 letters. Four of the eight eyes demonstrated CME by OCT on preoperative examination. There were no significant postoperative complications other than one eye that had a successful repair of an RD. At 3 months, the mean visual acuity was 54 letters. At last follow-up (mean, 10 months), the mean visual acuity was 61 letters ( P = .5). The final mean visual acuity change for the patients who had only one prior OPT (five eyes) was +10 letters. The mean final visual acuity change for the patients who had multiple OPT sessions (three eyes) was −1 letter. Three of the four eyes that had preoperative CME continued to demonstrate CME at last follow-up. Two eyes that had concurrent cataract extraction surgery with MTS360 did not develop CME. No eyes developed a recurrent CNV during the postoperative period. Conclusions MTS360 with silicone oil tamponade for CNV associated with ARMD appears to be a viable option for patients who are continuing to lose vision in their better seeing eye following OPT with verteporfin. MTS360 appears to be effective in stabilizing vision, especially in patients who had previously undergone only one OPT session. Further studies are indicated to evaluate the efficacy of MTS360 in this current era of OPT.

Ocular photodynamic therapy for serous macular detachment in the diffuse retinal pigment epitheliopathy variant of idiopathic central serous chorioretinopathy

Purpose To describe the anatomical and functional outcome of verteporfin ocular photodynamic therapy (PDT) in serous retinal detachment caused by the diffuse retinal pigment epitheliopathy form of chronic idiopathic central serous chorioretinopathy. Design Interventional case report. Method A 48-year-old Caucasian man with unilateral exudative retinal detachment from diffuse retinal pigment epitheliopathy and visual acuity of 20/40 was managed with verteporfin PDT applied sequentially in three separate spots targeting all retinal pigment epithelium leaks identified with intravenous fluorescein angiography (IVFA). Outcome measures included visual acuity, biomicroscopic appearance, and leakage on IVFA. Setting Clinical practice. Results Subretinal fluid resolved within 2 weeks; visual acuity returned to 20/20 with no recurrence at 6 months of follow-up. There was no leakage on IVFA posttreatment and no obvious toxicity. Conclusion To our knowledge, this is the first report of PDT causing resolution of macular detachment in diffuse retinal pigment epitheliopathy. Its long-term results with regard to the prognosis of the disease and the recurrence rate remain to be evaluated.

Clinicopathologic study after submacular removal of choroidal neovascular membranes treated with verteporfin ocular photodynamic therapy

PurposeTo report the clinicopathologic findings after submacular removal of choroidal neovascular membranes (CNV) treated with verteporfin ocular photodynamic therapy. DesignInterventional case series. MethodsRetrospective review of eight eyes of eight patients who underwent submacular surgery for CNV after having previously received verteporfin ocular photodynamic therapy for presumed ocular histoplasmosis (one patient), age-related macular degeneration ([AMD] three patients) pathologic myopia (two patients), punctate inner choroiditis (one patient), and idiopathic CNV (one patient). All cases had undergone ocular photodynamic therapy with verteporfin using standard protocols. Six of eight patients suffered a submacular hemorrhage after ocular photodynamic therapy, and two of eight patients refused further ocular photodynamic therapy. All patients subsequently had submacular surgery with removal of the CNV. One membrane was routinely processed, sectioned, and stained with hematoxylin and eosin. Five membranes were stained with toluidine blue for light microscopic examination. Semithin (1.0 μm) sections were cut and stained with uranyl acetate-lead citrate for transmission electron microscopy. ResultsChoroidal neovascular membranes were removed at 3 days (presumed ocular histoplasmosis), 29 days (punctate inner choroiditis), 63 days (AMD, pathologic myopia), 66 days (AMD), 107 days (pathologic myopia), 116 days (AMD), and 152 days (idiopathic) after verteporfin ocular photodynamic therapy. Histopathologic and ultrastructural examination showed areas of vascular occlusion at 3 days that were not seen at later time points. All specimens had patent CNV. There were signs of vascular damage with extravasated erythrocytes and fibrin, pigment clumping in cells, and inflammatory cells in all but the 3-day specimen. ConclusionsThis case series presents data only from patients who refused repeat treatment with ocular photodynamic therapy or who developed submacular hemorrhage after initial photodynamic therapy. Histopathologic evaluation of CNV 3 days after verteporfin ocular photodynamic therapy showed partial vascular occlusion that was not present in later specimens. These later specimens demonstrated evidence of vascular damage. Verteporfin ocular photodynamic therapy does not appear to lead to permanent and complete occlusion of the CNV. Thus, treatments that lead to permanent closure of CNV without damage to the retinal pigment epithelium and sensory retina are still needed.

Ocular Photodynamic Therapy.

Ocular Photodynamic Therapy.

Clinical Applications of the Organic Dye Laser

Clinical research utilizing the yellow, orange and red wavelengths of the dye laser (Rhodamine 6G and MD-631) indicates that the liquid organic dye laser may have considerable applications in ocular photodynamic and photocoagulation therapy. The effectiveness of the dye laser as a photodynamic (photoradiation) and photocoagulation source is due to the large numbers of wavelengths of relatively high output power that can be produced in the visible spectrum. Therefore, a target tissue can be selectively destroyed with minimal laser energy necessarily transmitted through the refractive media. The dye laser, as a photoradiation or photocoagulation system, should prove valuable in the therapy of ocular disease.