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TRANSPUPILLARY THERMO THERAPY: An Emerging and Promising Treatment Modality in Subfoveal Choroidal Neovascular Membrane
LALIT VERMA, HK TEWARI, SANJEEV NAINIWAL, JAYARAM RAVINDRANATHAN
Dr. Rajendra Prasad Centre of Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi - 29, India.
Transpupillary thermo therapy has been described as an alternative therapy to PDT for subfoveal CNVM secondary to ARMD. It is a large spot size, low irradiance, long exposure therapy. Studies have reported a closure of membranes in 77% of cases. This review article explains the mechanism, describes the procedure and summarizes the clinical trial of this modality of treatment.
Age related macular degeneration (AMD) is one of the leading causes of bilateral irreversible severe visual loss in individuals over 50 years of age due to formation of choroidal neovascularization (CNV) between retinal pigment epithelium (RPE) and Bruch’s membrane or subretinal space.[1-4] Laser photocoagulation is considered as the preferred treatment modality for extrafoveal and juxtafoveal classic CNV. However, because of the deleterious effects of the laser to the neurosensory retina, and also its limitations to treat only the extrafoveal and/or juxtafoveal CNV, clinicians have now shifted to various new treatment options for subfoveal CNV lesions like photodynamic therapy[5-8] (PDT), transpupillary thermotherapy[9,10] (TTT), radiotherapy,[11] interferon alpha-2,[12] macular rotation[13,14] and submacular excision of membrane[15] (Table 1). Of these the most promising are PDT and TTT.
PDT has undergone phase I, II and III trials showing an improvement of the visual acuity in 67% cases compared to placebo,[8] but is not free of the side effects caused by injection of visudyne dye. Moreover, the therapy is too expensive and very difficult to afford specially in view of the overall visual benefit, if at all, gained by the patient. Laser photocoagulation has been described to treat subfoveal CNV secondary to AMD, but it has several limitations like; it is effective in only a small percentage (10-15%) of cases who have a well defined CNV with distinct margins,[16] there may be an immediate significant fall in the central vision, evolution of a dense central scotoma and high rate of recurrence following laser treatment. The reported results of submacular and macular surgeries have also not been very satisfactory[13-15] especially in choroidal neovascular membranes secondary to AMD. These results compare with natural history of occult CNV in ARMD, i.e. 63% suffer visual loss > 3 lines over six months[17] and 41% suffer severe visual loss (SVL) within 12 months[17] (decrease of >- 6 lines).
Treatment options for subfoveal SRNVM's* Photodynamic therapy (PDT) * Transpupillary thermo therapy (TTT) * Macular rotation surgery * Interferon - 2 alpha * Oral thalidomide * Gene therapy
TTT has recently been described as an alternative form of therapy for subfoveal CNV secondary to AMD. It is a large spot size, low irradiance, long exposure infrared laser therapy that is primarily used to treat occult CNV secondary to AMD.[9] Unlike laser photocoagulation, which produces coagulation (i.e. denaturation of proteins), the aim of treatments in TTT is to produce an intralesional temperature rise of 4-9°C, though the exact mechanism of action is still unclear. The probable one is vascular thrombosis precipitated by cytotoxic free radicals released from irradiated tissue. Relatively rapid involution of CNV following TTT prevents subretinal scarring and permanent photoreceptor damage, thereby prevent central and permanent scotoma in patients with subfoveal CNV. Reichel et al[9] in his initial study on 16 eyes of 15 cases reported an improvement of the visual acuity in 19% and stabilization in 56% cases with no overt complications and decreased exudation in 94% of cases upto an average of 11 months after TTT. Similarly, Newsom et al[10] in 2001 reported closure of the membranes in 77% (34/44) of cases with stabilization of the visual acuity in 47.7% (21/44) and improvement in 9% (4/44) of the cases upto an average of 6.1 months after TTT. Okada[18] in 2000 presented improvement of the visual acuity in 5% (1/20), and stabilization in 75% (15/20) with decreased exudation in 75% (15/20) eyes after a mean of 8.75 months after TTT.
The parameters to assess before the TTT are: visual acuity by ETDRS chart, scotoma score recording on Amsler grid chart, fundus examination by direct and indirect ophthalmoscope as well as by slit-lamp biomicroscopy using +90 D lens followed by fundus photography and fluorescein angiography (FA) on digital fundus camera.
TTT is performed under topical anaesthesia (1.5% proparacaine eye drops) with an OcuLight 810 nm diode laser (Iridex) modified for large spot size and long exposure time with slit-lamp adaptor. Spot size should encompass the entire lesion (ranging from 0.8 mm - 3.0 mm).
Treatment is given for 60 seconds, the end point being no visible change or slight graying of the retina. Goldman type lens with anti-reflective coating is usually used and laser targeting is achieved by a diode red beam.
Patients are followed up at six weeks and 12 weeks after TTT. At each follow-up visit, ETDRS visual acuity, scotoma score, and fundus examination is performed with fundus photography and FA. Retreatments can be given to the patients who retain the active CNV on FA for more than six weeks after TTT.
In our initial experience of treatment subfoveal CNVMs secondary to AMD, visual acuity gets stabilized in 20% (6/30) and improves in 60% (18/30) eyes, whereas, 20% (6/30) eyes showed a decrease of the vision at three months after TTT. These results are being comparable to the above-mentioned studies. In addition to the visual acuity, we also recorded the scotoma score (SS) as well as reading speed (RS) before and after TTT, which have not been reported in the earlier studies. We found that the mean scotoma score recorded using Amsler grid chart decreased from a pre TTT value of 47.56 to 37 at 12 weeks after TTT.
Similarly, the mean reading speed recorded in words/minute showed a slight increase from 27.04 to 37.33 at 12 weeks after TTT.
TTT is an effective and promising method to treat subfoveal CNV in AMD,[9,10] a fact also reflected in our study. This is associated with stabilisation or improvement of visual acuity in over 80% of patients (our study), along with decrease in scotoma size and increase of reading speed.
The classic indications of TTT are occult CNV defined on fluorescein angiography as fibrovascular retinal pigment epithelial detachment (RPED) showing irregular stippled hyperfluorescence in mid-phase with leakage/staining in late phase or late phase leak of undetermined source. However, in our set-up, where PDT is either not easily available or very expensive, we did not differentiate between classic and occult CNV. Our sole criteria for inclusion in the present study was subfoveal CNV secondary to AMD.
Though TTT has some advantages (Table 2) over other treatment modalities (PDT, laser photocoagulation etc.), its treatment variables have not been completely elucidated (Table 3). The end point is difficult to determine clinically. The treatment parameters may need to be adjusted according to variables like: age of the patient, pigmentation, media clarity (phakic/pseudophakic), retinal oedema, haemorrhages, and location of CNV. However, TTT has many advantages over other treatment options: it is well-tolerated and inexpensive therapy, there are no systemic side effects or restrictions, results are reproducible and the collateral damage to the adjacent retina is less.
Advantages of transpupillary thermotherapy* Efficacious * Dries up macula (80%) * Well tolerated * No systemic side effects/restrictions * Reproducible results * Less collateral damage to adjacent retina
Problems with transpupillary thermotherapy* Problems in power caliberation for an individual patient
----Lot of variables
----Age
#Pigmentation
#Media clarity (Phakic, Psuedophakic)
#Retinal Oedema haemorrhage, elevation
----Western standards of power used is not suitable for Indian population* Difficulty in treating lesions larger than 3 mm
In the West, standard power for 3 mm spot size is 800-mW for 60 seconds (Table 4). But this power is too high for Indian pigmented eyes and certainly may lead to a retinal burn. It should be either no reaction or minimal colour change at the level of RPE. As far as our experience from the study in Indian eyes, 400-450 mW power for a 3 mm spot size seems optimal. The absolute power value for individual eyes should vary subject to above mentioned variables. One method suggested for calculating optimal power is to put a test burn for 60 seconds in the nasal retina, find threshold and reduce power by 10%. However, this also has its limitations viz area to be treated usually has oedema, haemorrhages etc., whereas test burn is placed on healthy looking retina.
Transpupillary thermotherapy
(Laser power selection for 60 seconds exposure)
The precise role of TTT in treatment of CNV needs to be further defined. However clinical improvement, high closure rate, minimal recurrence, reproducible results, no post-treatment restrictions (like light exposure, full sleeves clothes, wide brim hat, etc.) and most important, cost effectiveness of treatment suggest the improvement role that TTT may play in the treatment of sub foveal CNVs especially in an Indian perspective. However, still long term multicentric prospective, randomized controlled trials are required to further clarify the role of TTT in the treatment of CNV.
Our study supports the role that TTT can play in the management of subfoveal CNV secondary to AMD. We conclude that TTT is not only a cheap alternative to PDT, but also an efficacious tool in stabilization or improvement of visual acuity.
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