Laser treatment for choroidal melanoma: Current concepts

Laser treatment has offered a relatively nonsurgical alternative for eye, life, and vision-sparing treatment of malignant melanoma of the choroid. Historically, the most commonly used forms of lasers were xenon-arc, argon laser, krypton laser, and the more recent transpupillary thermotherapy (TTT) and photodynamic therapy (PDT). Melanomas selected for laser treatment tend to be smaller and visibly accessible, which means these tumors are usually located in the posterior choroid. Laser treatments have been associated with both local tumor destruction and side effects. Unlike radiation therapy, laser treatment has been commonly associated with retinal traction, hemorrhage, chorioretinal neovascularization, and extra scleral tumor extension, as well as higher rates of local treatment failure. In addition, however, laser-treatment has been successfully used to treat tumor-related retinal detachments, radiation retinopathy, and neovascular glaucoma. We review the world's experience of ophthalmic laser treatment for choroidal melanoma, offer safety and efficacy guidelines, as well as a comparison of laser treatment to radiation therapy outcomes.     

Low vision aid in exudative macular degeneration treated by photodynamic therapy and thermal laser photocoagulation

To determine the efficacy of low vision rehabilitation (LVR) in patients with age-related macular degeneration (AMD) treated by photodynamic therapy (PDT) compared to those treated by thermal laser photocoagulation (TLP). · METHODS: A retrospective study was performed examining the files of 42 patients (42 eyes) with AMD who had been treated either by TLP (Group 1) and PDT (Group 2). Once AMD was considered to be inactive they underwent visual rehabilitation in the LVR Unit in order to increase their ability for distant and near vision. · RESULTS: Eighteen eyes had received PDT and 24 had received TLP. Average corrected visual acuity after laser therapy was 0.14 in Group 1, and 0.16 in Group 2. No statistically significant differences were found between both groups before and after laser therapy. Both groups showed improvement after LVR; however, statistically significant differences between both groups were found only for near vision. · CONCLUSION: Our findings suggest that even though both PDT and TLP are associated to a decreased visual acuity after treatment, LVR may be more successful for near vision among patients treated by PDT     

光动力治疗和热激光光凝治疗渗出性黄斑变性所致低视力

目的:比较观察光动力治疗(PDT)和热激光光凝(TLP)治疗对年龄相关性黄斑变性(AMD)患者低视力(LVR)的临床疗效。方法:对 42 例(42 眼)AMD 患者资料进行回顾性研究,其分别行 TLP 治疗(组 1)或 PDT 治疗(组 2)。一旦确定 AMD 处于非活动期,患者在 LVR 部进行视力康复,以提高其远、近视功能。结果:18 眼接受了 PDT 治疗,24 眼进行 TLP 治疗。激光治疗后,组 1 患者的平均最佳矫正视力为0.14,组 2 平均为 0.16。两组比较,视力于激光治疗前后都没有统计学差异;两组的 LVR 都有提高,但两组中只有近视力比较有统计学差异。结论:本研究结果表明,PDT 和 TLP 治疗后患者的视力均有所下降,PDT 治疗时,LVR 患者近视力改善更为有效。     

Application of femtosecond ultrashort pulse laser to photodynamic therapy mediated by indocyanine green

BACKGROUND/AIMS: To evaluate treatment with high peak power pulse energy by femtosecond ultrashort pulse laser (titanium sapphire laser) delivered at an 800 nm wavelength for corneal neovascularisation using photodynamic therapy (PDT) mediated by indocyanine green (ICG). METHODS: Using a gelatin solid as an in vitro corneal model, the safety of laser power was studied to determine if it degenerated gelatin with or without ICG. The authors then induced corneal neovascularisation in rabbit eyes by an intracorneal suturing technique. Fluorescein angiography was used to evaluate occlusion before PDT and 0, 1, 3, and 10 days after PDT. The authors performed light microscopy with haematoxylin eosin staining and transmission electron microscopy to determine thrombosis formation in the neovascular regions. RESULTS: The threshold of peak laser power density ranged from 39 to 53 W/cm(2). Laser irradiation was started 30 seconds after a 10 mg/kg ICG injection, and all irradiated segments were occluded at 0, 1, 3, and 10 days at 3.8 J/cm(2). Light and electron microscopy documented thrombosis formation in the neovascular region. CONCLUSION: Femtosecond pulse laser enhanced by ICG can be used for PDT. Because of effective closure of corneal neovascularisation at a low energy level, the high peak power pulse energy of the femtosecond pulse laser might be more efficacious than continuous wave laser for use with PDT.     

Ocular phototherapy

Phototherapy can be translated to mean ‘light or radiant energy-induced treatment.'' Lasers have become the exclusive source of light or radiant energy for all applications of phototherapy. Depending on the wavelength, intensity, and duration of exposure, tissues can either absorb the energy (photocoagulation, thermotherapy, and photodynamic therapy (PDT)) or undergo ionization (photodisruption). For phototherapy to be effective, the energy has to be absorbed by tissues or more specifically by naturally occurring pigment (xanthophyll, haemoglobin, and melanin) within them. In tissues or tumours that lack natural pigment, dyes (verteporphin, Visudyne) with narrow absorption spectrum can be injected intravenously that act as focal absorbent of laser energy after they have preferentially localized within the tumour. Ocular phototherapy has broad applications in treatment of ocular tumours. Laser photocoagulation, thermotherapy, and PDT can be delivered with low rates of complications and with ease in the outpatient setting. Review of the current literature suggests excellent results when these treatments are applied for benign tumours, particularly for vascular tumours such as circumscribed choroidal haemangioma. For primary malignant tumours, such as choroidal melanoma, thermotherapy, and PDT do not offer local tumour control rates that are equivalent or higher than those achieved with plaque or proton radiation therapy. However, for secondary malignant tumours (choroidal metastases), thermotherapy and PDT can be applied as a palliative treatment. Greater experience is necessary to fully comprehend risks, comparative benefits, and complication of ocular phototherapy of ocular tumours.     

Incidence of laser photocoagulation and photodynamic therapy with verteporfin at a tertiary retinal center

PURPOSE: To examine the influence of photodynamic therapy (PDT) with verteporfin on the indication and frequency of conventional thermal krypton laser photocoagulation in choroidal neovascularization. METHODS: A retrospective chart review was performed comparing laser indication and frequency 1 year before and 2 years after PDT started to be used routinely following the guidelines of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study Group and the Verteporfin in Photodynamic Therapy Study Group. RESULTS: Similar frequencies of laser treatment were seen in the year before and during the first year after PDT was commenced (301 [7.1% of all patients] to 281 [6.9%]). In the year thereafter, however, there was a marked decrease in laser treatments (174 [3.9%]). Interestingly, there was a steady increase in the relative frequency of laser treatments of extrafoveal and parapapillary lesions in the years after PDT was commenced (29.2%, year 1; 30.6%, year 2; and 39.6%, year 3). CONCLUSION: PDT has led to a decrease in conventional laser photocoagulation at one large tertiary retinal center in Austria. Moreover, it is our belief that patients are now referred at earlier stages of the disease, which has resulted in a shift in thermal laser indications.     

兔眼脉络膜黑色素瘤的第二代光敏剂光动力治疗

目的 观察第二代光敏剂CASPc（chloroaluminum su lfonated phthalocyanine,CASPc）对B16F10黑色素瘤动物模型的光动力治疗（PDT）作用 。 方法 38只新英格兰大白兔经免疫抑制后种植B16F10黑色素瘤碎片于脉络膜下腔，B型超声、间接检眼镜随访肿瘤生长至2.0 ~3.8 mm厚时30只兔眼给予PDT治疗。耳静脉注射CASPc 5 mg/kg, 24 h后给予氩-染料激光照射，激光波长675 nm, 输出功率600 nm/cm2，激光照射剂量20~70 J/cm2；8只对照组兔眼只给予激光或光敏物质。治疗后观察6~8周。 结果 38只兔眼建模成功。30只PDT治疗兔眼中21只眼肿瘤得到控制，9只眼未能控制；对照组兔眼肿瘤治疗后2周充满整个玻璃体。 结论 第二代光敏剂CASPc对实验性眼B16F10黑色素瘤具有一定的PDT治疗作用。 （中华眼底病杂志，2004，20：67-132）     

Russian photosensitizer radachlorine in photodynamic therapy for epibulbar and choroid tumors: experimental studies

The authors used the Russian agent Radachlorine as a photosensitizer (PS) in photodynamic therapy (PDT) for epibulbar and chorioid tumors. Analyzing the results suggests that the efficacy of Radachlorine used as PS in a correctly adjusted dose in PDT may be high. The optimization of effects in the experiment was observed when Radachlorine was used in a dose of 3 mg/kg with a light radiation dose of 500 mW/cm2 upon 5-min exposure. However, a rapid relapse in some cases indicates the instability of the effect and makes it necessary to make repeated PS injections and PDT sessions.     

Subretinal neovascular membrane associated with type 2a idiopathic juxtafoveolar telangiectasis in pseudoxanthoma elasticum

Background The objective was to report a case of pseudoxanthoma elasticum associated with type 2A idiopathic juxtafoveolar telangiectasis (T2AIJT) complicated by bilateral subretinal neovascular membranes (SRNVM). Methods The right eye with juxtafoveal SRNVM and the left eye with subfoveal SRNVM underwent laser photocoagulation and photodynamic therapy respectively. The follow-up duration was 48 months. Results Best corrected visual acuity was 20/32 in both eyes at baseline, and 20/32 in the right eye and 20/200 in the left eye at the end of the follow-up. Atrophic changes in the retinal pigment epithelium developed around the SRNVM treated with photodynamic therapy (PDT). Conclusions Pseudoxanthoma elasticum may be associated with T2AIJT complicated by bilateral SRNVM. Further studies are needed to assess both efficacy and appropriate PDT regime in T2AIJT-related SRNVM, especially if associated with other conditions.     

Longstanding symptomatic choroidal hemangioma managed with limited PDT as initial or salvage therapy

Purpose To describe the use of limited, low-irradiance, single-spot photodynamic therapy (PDT) with verteporfin for the treatment of symptomatic choroidal hemangiomas.Methods Thirteen consecutive patients with a circumscribed choroidal hemangioma were treated with limited PDT 6 min following a 1-min infusion with verteporfin (6 mg/m² body surface area), using a diode laser (692 nm) and a single spot large enough to cover only the most prominent part of the tumor. Exposure time was 166 s in the first three patients and 83 s in the last ten patients, resulting in a radiance exposure of respectively 100 and 50 J/cm².Results In all 11 not previously conventionally treated patients, visual acuity improved following PDT treatment. The two remaining patients with prior radiation treatment both reported widening of the visual field and sharper vision, but did not show an increase in ETDRS vision. In all but four patients the tumor became ultrasonographically undetectable by the first follow-up visit at 6 weeks, with only a slight irregularity at the level of the previous tumor remaining. In four patients the residual tumor was still detectable, and they received a second treatment, following which the tumor flattened completely. In all patients the retinal detachment disappeared.Conclusion The present series demonstrates that even limited, low-irradiance, single-spot photodynamic therapy with verteporfin is an effective first-line treatment for choroidal hemangiomas.Financial support/proprietary interest: none     

Combined photodynamic therapy and intravitreal ranibizumab as primary treatment for subretinal neovascular membrane (SRNVM) associated with type 2 idiopathic macular telangiectasia

Background To report the efficacy of combination photodynamic therapy and intravitreal ranibizumab for juxtafoveal, subretinal neovascular membrane (SRNVM) associated with type 2 idiopathic macular telangiectasia (IMT). Methods A 56-year-old woman with visual loss due to SRNVM secondary to IMT underwent primary treatment with a combination of photodynamic therapy (PDT) and intravitreal ranibizumab (0.5 mg). PDT was done as per the TAP study protocol, except that the laser spot size was same as the greatest linear diameter (GLD) of the lesion. This was followed by intravitreal ranibizumab (0.5 mg), 2 days later. Results At the 16-week follow-up, clinical examination revealed regression of the SRNVM, with no evidence of subretinal fluid, exudates or fresh hemorrhages. Visual acuity improved by 2 Snellen lines (from 6/36 to 6/18). Clinical findings were confirmed on FFA and OCT. At the last follow-up at 9 months, the SRNVM remained quiescent and visual acuity stable. No treatment-related adverse effects were noted. Conclusion Combination therapy with PDT and intravitreal ranibizumab appears to be efficacious in the treatment of SRNVM associated with proliferative type 2 IMT. The authors have full control of all primary data and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request. There are no funding or other conflicts of interest.     

Photodynamic therapy with verteporfin for anterior segment neovascularizations in neovascular glaucoma

PURPOSE: To evaluate photodynamic therapy (PDT) with verteporfin for iris and angle neovascularization in eyes with neovascular glaucoma. DESIGN: Interventional case series. METHODS: A prospective, noncomparative case series included four patients (four eyes) with neovascular glaucoma. PDT was performed following the parameters of treatment of age-related macular degeneration with photodynamic therapy Study Group (TAP). The laser was directed at the anterior chamber angle and iris surface using a Goldmann three-mirror contact lens. Iris and angle neovascularization were quantified using the number of clock hours involved. Outcome measures were obliteration of neovascularization and decrease of intraocular pressure (IOP). RESULTS: One week after PDT, we registered complete obliteration of angle neovascularization and partial occlusion of iris neovascularization. Subsequent reopening of angle neovascularization was detectable at 1 month. Intraocular pressure diminished considerably after 1 week, with a subsequent tendency toward stabilization. CONCLUSIONS: Photodynamic therapy can be used safely and effectively in the early phases of neovascular glaucoma to achieve angle neovascularization obliteration and IOP reduction.     

Indications for photodynamic therapy in age-related macular degeneration

Exudative age-related macular degeneration (ARMD) is now benefitting from new therapeutic approaches. Three international randomized clinical trials have demonstrated the efficacy of photodynamic therapy (PDT) in stabilizing visual acuity at 2 years. PDT is based on the activation of a photosensitizer with an adapted wavelength. In age-related macular degeneration, the photosensitizer used is verteporfin (Visudyne), which accumulates preferentially in choroidal new vessels. Functional results are obtained on the basis of a strict classification based on fluorescein angiography examining the type of the new vessels responsible for exudative ARMD. Thus, subfoveal lesions, either predominantly classic (>50%) or occult only, are the indication for PDT. Classic CNVs where laser photocoagulation thermal burns extend into the foveola may be an extrapolation of the indication for PDT. In addition, fluorescein angiography is essential for considering retreatment, usually necessary. Demonstrated growth and the persistence of leakage from the CNV is an absolute indication for a new session of PDT. A number of features still require assessment in order to define the responder group more accurately and to refine and possibly simplify the indications for retreatment.     

RPE atrophy following photodynamic therapy in type 2A idiopathic parafoveal telangiectasis

We report a case of Type 2A idiopathic parafoveal telangiectasis treated by Photodynamic Therapy (PDT), resulting in retinal pigment epithelial (RPE) atrophy corresponding to the size of the laser spot used. This raises a doubt regarding the safety of photodynamic therapy in CNVM secondary to type 2A parafoveal telangiectasis.     

PDT to monkey CNV with ATX-S10(Na): inappropriateness of early laser irradiation for selective occlusion

PURPOSE: There is controversy about which mode of laser irradiation, early irradiation with low-dose photosensitizer or late irradiation with high-dose, benefits the selective occlusion of choroidal neovascularization (CNV) in photodynamic therapy (PDT). In this study, using an amphiphilic photosensitizer, 13,17-bis (1-carboxypropionyl) carbamoylethyl-8-etheny-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetraethyl porphyrin sodium (ATX-S10(Na); Photochemical Inc., Okayama, Japan), photodynamic and adverse effects of early irradiation on CNV-bearing monkey eyes were investigated. METHODS: Experimentally induced CNV lesions and normal retina were irradiated with a diode laser (670-nm wavelength) at a dose of 1 to 90 J/cm(2) at 1 to 19 minutes after intravenous injection of 2 mg/kg body weight of ATX-S10(Na). Vascular occlusion and CNV recurrence were evaluated by fluorescein and indocyanine green angiography and histologic analysis, until 4 weeks after irradiation. RESULTS: Of 45 different conditions, 23 did not induce CNV closure, 20 provided both CNV occlusion and retinal vessel damage, and 2 achieved selective CNV occlusion without retinal vascular injury. Recurrence of CNV was induced in 19 of 22 CNV-occluding conditions. ATX-S10(Na) angiography showed that dyes were similarly distributed between normal vessels and CNV at early time periods after injection, whereas they were preferentially accumulated in CNV after 30 minutes. CONCLUSIONS: In PDT with ATX-S10(Na), irradiation within 20 minutes of dye injection failed to induce selective CNV occlusion, probably because there is no significant difference in the biodistribution of dye between CNV and retinal vessels. It also caused frequent CNV recurrence after extensive inflammation in the irradiated retina.     

Effect of axial length on laser spot size during photodynamic therapy: an experimental study in monkeys

PURPOSE: To investigate the effect of shorter axial length on the laser spot size and laser energy during photodynamic therapy (PDT) in monkeys. DESIGN: Experimental study with four rhesus monkeys. METHODS: PDT was performed on the normal retina of monkeys whose ocular axial lengths are shorter (19.55 to 20.25 mm) than that of humans. After the PDT, the eyes were enucleated, and the diameter of the irradiated laser spot was measured with a microcaliper. RESULTS: The area of actual laser spot was only 0.56 to 0.61 times of the planned area, which indicated that the laser energy/area was 1.64 to 1.78 times more intense than planned initially. CONCLUSION: These results are the in vivo demonstration that the diameter of PDT laser spot is smaller for eyes with shorter axial lengths.     

Photodynamic monotherapy or combination treatment with intravitreal triamcinolone acetonide, bevacizumab or ranibizumab for choroidal neovascularization associated with pathological myopia

This retrospective, interventional case series analyses treatment outcomes in eyes with choroidal neovascularization (CNV) secondary to pathological myopia, managed with photodynamic therapy, (PDT), (Group 1, N = 11), PDT and intravitreal triamcinolone acetonide (4 mg/0.1ml) (Group 2, N = 3), PDT and intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab 1.25 mg/0.05 ml, ranibizumab 0.5 mg/0.05 ml and reduced-fluence PDT and intravitreal ranibizumab 0.5 mg/0.05 ml (Group 3, N=12). All the patients underwent PDT. Intravitreal injections were repeated as required. SPSS 14 software was used to evaluate the data. Wilcoxon signed ranks test was used to evaluate pre- and post-treatment vision. The Kruskal-Wallis test was used for comparison between the groups. All the groups were statistically comparable. All the eyes showed complete regression of CNV, with a minimum follow-up of six months. All groups had visual improvement; significantly in Group 3 ( p = 0.003). Combination PDT with anti-VEGF agents appeared to be efficacious in eyes with myopic CNV. However, a larger study with a longer follow-up is required to validate these results.     

Photodynamic therapy in age-related macular degeneration--results of one year observation

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) with verteporfin in reducing the vision loss and progression of choroidal neovascularization (CNV) in patients with subfoveal CNV due to age-related macular degeneration (AMD). MATERIALS AND METHODS: 46 eyes of 46 patients with subfoveal, predominantly classic CNV caused by AMD and best-corrected visual acuity of 5/50 to 5/10 were treated with photodynamic therapy with verteporfin (Visudyne, CIBA Vision). Verteporfin was administered via intravenous infusion over 10 minutes. Fifteen minutes after the start of the infusion, a diode laser light at 689 nm (Opal Photoactivator, Coherent) was delivered over 83 seconds. Visual acuity and fluorescein angiography were performed before and after the treatment at 7 days and 1, 3, 6, 9 and 12 months after the initial-treatment. Retreatment in the same manner was applied if at follow-up examination fluorescein leakage from CNV was seen. Outcomes were compared with those of control group which consisted of 38 eyes of 38 patients of the same condition of the disease, not treated with any method. RESULTS: The lost of visual acuity was significantly reduced in the verteporfin--treated eyes compared--with controls. At the 12 month 73.91% eyes of PDT group versus 36.84% of control group (p < 0.001) lost fewer than 3 Snellen lines. The vision loss appeared to be more rapid in first 6 months of the study. During the study growth of CNV was diminished in PDT group compared with control group. CONCLUSIONS: Results show, that photodynamic therapy may be an effective method of treatment for predominantly classic subfoveal choroidal neovascularization caused by AMD. Further studies are needed to find the best modes of PDT procedure.     

Dynamic phototherapy: treatment and retreatment criteria

Exudative age-related macular degeneration (ARMD) is benefiting at present from new therapeutic approaches. Randomized clinical trials have demonstrated the efficacy of photodynamic therapy (PDT) in stabilizing visual acuity at 3 years. The basis of PDT consists in activating a photosensitizer with an adapted laser wavelength. Functional results are obtained on the basis of a strict classification of type of the new vessels responsible for exudative ARMD, based on fluorescein angiography. Thus, subfoveal lesions, in the form of either predominantly classic (visible new vessels>50%) or occult choroidal neovascularization (CNV), are the only indication for this therapy. Classic juxtafoveal CNV, where laser photocoagulation thermal burns may extend into the foveola, may be an extension of the indication of PDT. The follow-up after PDT is based on fluorescein angiography findings. The extension and persistence of leakage from the CNV remains an indication for retreatment. Ongoing studies are evaluating a number of features in order to define the responder group and possibly simplify the retreatment indications.     

光动力疗法治疗老年性黄斑变性的临床研究

目的
观察光动力疗法(photodynamic therapy,PDT)对渗出型老年性黄斑变性(age-related macular degeneration,AMD)脉络膜新生血管(choroidal neovascularization,CNV)进行单次和多次治疗的临床疗效。
方法
20例经双目间接立体检眼镜、荧光素眼底血管造影(fundus fluorescein angiography, FFA)、吲哚青绿血管造影(indocyanine green angiography, ICGA)检查确诊的AMD患者的31只患眼纳入治疗。患者年龄47～88岁，平均年龄68.1岁，最佳矫正视力在数指/10 cm～0.6之间。光敏剂苯并卟啉衍生物单酸(benzoporphyrin derivative mono acid, BPD)(中国诺华公司)6 mg／m 2静脉滴注10 min，开始静脉用药后15 min，通过裂隙灯用强度为50 J／cm2的689 nm激光(德国Zeiss公司)照射83 s。治疗后患者尽可能避光48 h。治疗后2周开始复查，每3个月随访1次，随访时间最短3个月，最长18个月，平均随访12个月。FFA和(或)ICGA显示病灶范围扩大、或渗漏增加，即进行重复PDT治疗。其中1只眼进行了4次治疗, 4只眼进行了2次治疗，其余26只眼均只进行了1次治疗。
结果
治疗后13只眼视力明显改善(视力提高≥2行)，占41.9%；17只眼视力稳定不变(视力波动在1行以内)，占54.8%；1只眼视力下降2行，占3.2%。所有患眼于PDT治疗后眼底出血和渗出均减轻；FFA或FFA+ICGA检查显示：PDT治疗后2周，CNV的渗漏明显减少或完全停止，复发或扩大的CNV经多次PDT治疗后，渗漏逐渐减少，3例5只眼渗漏完全停止。光相干断层成像术(optic coherence tomography, OCT)检查显示CNV周围视网膜脉络膜的水肿以及神经上皮脱离、色素上皮脱离明显好转。20例患者在PDT治疗过程中及治疗后未发生任何全身和局部不良反应。
结论
单次和重复PDT治疗可以部分或完全封闭AMD 的CNV，多次PDT治疗可以封闭CNV，降低AMD引起视力下降的危险性。PDT治疗不影响病灶周围的正常视网膜和脉络膜组织，对视力无损害。
(中华眼底病杂志, 2002, 18: 175-179)