|
 |
| ORIGINAL ARTICLE |
|
| Year : 2004 | Volume
: 52
| Issue : 1 | Page : 35-40 |
|
Transpupillary thermotherapy in subfoveal choroidal neovascular membrane secondary to age-related macular degeneration
L Verma, Hem K Tewari, S Nainiwal, J Ravindranathan
Centre for Ophthalmic Sciences, All Institute of Medical Sciences, New Delhi, India
Correspondence Address:
L Verma
Centre for Ophthalmic Sciences, All Institute of Medical Sciences, New Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 15132377 
Purpose: To report our initial experience in the treatment of subfoveal choroidal neovascular membrane, secondary to age-related macular degeneration (AMD) by transpupillary thermotherapy (TTT).
Methods: Fifty consecutive patients with subfoveal choroidal neovascularisation (CNV) secondary to AMD, were included in the study. The parameters assessed before the TTT were visual acuity by ETDRS chart, scotoma score by Amsler grid chart, reading speed, fundus examination by direct and indirect ophthalmoscope as well as +90 Diopter lens followed by digital fundus photography and fluorescein angiography (FA).
Results: The letter visual acuity improved or stabilized in 72% cases up to 12 weeks after TTT. Mean scotoma score decreased from a mean of 47.56, to 43.56 at 6 weeks and to 37 at 12 weeks. Mean reading speed increased from 27.04 words/minute at pretreatment to 34.52 words/minute at 6 weeks and 37.33 words/minute 12 weeks after TTT.
Conclusion: TTT is not only a cheaper alternative to photodynamic therapy (PDT), but also is an efficacious tool in stabilisation or improvement of visual acuity in the management of subfoveal choroidal neovascular membrane due to AMD.
Keywords: Transpupillary thermotherapy, age-related macular degeneration, choroidal neovascular membrane
How to cite this article:
Verma L, Tewari HK, Nainiwal S, Ravindranathan J. Transpupillary thermotherapy in subfoveal choroidal neovascular membrane secondary to age-related macular degeneration. Indian J Ophthalmol 2004;52:35-40 |
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 neovascularisation (CNV) between retinal pigment epithelium (RPE) and Bruch's membrane or subretinal space. [1],[2],[3],[4]Laser photocoagulation is considered the preferred treatment modality for extrafoveal and juxtafoveal classic CNV. However, because of the deleterious effects of the laser to the retina, and because its use is limited to treatment of the extrafoveal and/or juxtafoveal CNV, clinicians have now shifted to various new treatment options for subfoveal CNV lesions like photodynamic therapy[5],[6],[7],[8] (PDT) transpupillary thermo-therapy[9],[10] (TTT), radiotherapy,[11] interferon alpha-2,[12] macular rotation[13],[14] and submacular excision of membrane.[15] Of these the most promising are TTT and PDT.
TTT 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 causes denaturation of proteins, TTT aims at increasing the intralesional temperature by 4-9ºC. Though the exact mechanism of action is still unclear, a probability is the vascular thrombosis precipitated by cytotoxic free radicals released from the irradiated tissues. Relatively rapid involution of CNV following TTT prevents subretinal scarring and permanent photoreceptor damage, thereby preventing central and permanent scotoma in patients with subfoveal CNV.
We herein report our initial experience of TTT treatment of subfoveal CNV secondary to AMD in 50 Indian eyes.
| Material and Methods | |  |
Fifty consecutive patients with subfoveal CNV secondary to AMD, who presented to the Retina Service of our centre were included in the study. Patients who had other ocular disease, physical or mental disability, or who had received previous laser photocoagulation or any other treatment for subfoveal AMD were excluded from the study.
The parameters assessed before TTT were visual acuity by ETDRS chart, intraocular pressure (IOP) by applanation tonometry, anterior segment examination by slitlamp biomicroscope, scotoma score by the Amsler grid chart, reading speed, fundus examination by direct and indirect ophthalmoscope as well as +90 D (Volk) lens, followed by fundus photography and fluorescein angiography (FA).
The visual acuity was measured using the ETDRS chart. Initially the patient was asked to read the chart at 4 meters with one eye closed. If the patient was unable to read the uppermost line from 4 meters, he/she was asked to read it at 2 meters and then at 1 meter if he still couldn't identify the uppermost line from 2 meters. The number of letters read at each distance was noted as letter visual acuity. Improvement of vision was considered as gain in vision of more than 5 letters or one line and deterioration as loss of 5 letters. Stabilisation was considered as no change or less than 5 letters gain or loss in the ETDRS chart from the baseline visual acuity score.
The scotoma score was taken using the Amsler grid chart. The patient was asked to chart out the scotoma with the chart kept at 12 inches from the eye. The score was obtained by adding the small squares inside the charted scotoma. If the line went through the square at the edge of the scotoma, the square was counted only if it included more than half its area.
The reading speed was measured in the following way. A paragraph of about 40 words in large print, in Times Roman type, was selected from the Reader's Digest magazine. The patient was asked to read this at a convenient distance using spectacles or a low vision aid (LVA) if required, as used earlier by Ebert et al.16 Large letters measured 1.43 cm and small letters measured 0.95 cm. In a study conducted by Fine and associates, 91% of patients with neovascular ARMD with a visual acuity of 20/250 (6/75) or better were able to read the text.16 The patients were given 3 minutes to read the text and the total number of words were then divided by 3 to obtain the reading speed in words per minute.
On fluorescein angiography, the classic CNV was diagnosed as hyperfluorescence detected as a lacy network filling concurrently with the background choroidal fluorescence and increasing in area and intensity in the mid and late phases of FA. Occult CNV was diagnosed from either fibrovascular pigment epithelial detachment (at one to two minutes, stippled hyperfluorescent pigment dots noted on the surface of irregularly elevated RPE, not corresponding to drusen or RPE atrophy), or as late phase leakage from an undertermined source.
TTT parameters
TTT was performed under topical anaesthesia (1.5% proparacaine eye drops) in all patients with an OcuLight 810 nm diode laser (Iris Medical Oculight SLx, Iridex Corporation, Mountain View, CA, USA) modified for large spot size and long exposure time with a slitlamp adaptor. The spot size encompassed the entire lesion (ranging from 0.8mm-3.0mm) with 300-550 mW of power. Treatment was given for 60 seconds; the end point was either no visible change or slight graying of the retina. Goldman type lens of quadra-spheric lens with anti-reflective coating was used in every case.
Patients were followed up at 6 weeks and 12 weeks after TTT. At each follow-up visit, ETDRS visual acuity, scotoma score, reading speed, fundus examination, fundus photography and FA were repeated. Retreatments were given to the patients who retained an active CNV on FA for more than 6 weeks following TTT.
| Results | | |
The patients were between 45 and 84 years of age. Thirty three were males and 17 were females, and all had symptoms of visual loss and/or metamorphopsia within the last 3 months. Of the 50 patients studied, 36 had occult CNV and the remaining 14 had classic CNV on fluorescein angiography (FA). There was fluorescein angiographic evidence of subfoveal CNV with or without pigment epithelial detachment (PED).
The initial average ETDRS visual acuity was 25 letters (20/400) with post-treatment VA was 30 (20/320) at 6 weeks, remaining stable on 30 letters at 12 weeks. Of the 36 patients with occult CNV, visual acuity at 6 weeks after TTT got stabilised in 13, increased in 16 and decreased in 7 eyes. Of the 14 eyes with classic CNV, visual acuity stabilised in 3, increased in 4 and decreased in 7 eyes.
The mean visual acuity before TTT in the occult and classic CNV groups, was 28.27 and 39.52 respectively. After 12 weeks post-TTT, the visual acuity in the same groups was 33.77 and 35.28 respectively. On an average, the mean letter visual acuity before TTT was 23.88, which improved to 35.13 at 12 weeks after TTT [Figure - 1].
Mean scotoma score recorded using Amsler's grid chart showed an average pretreatment score of 47.56, decreasing to 43.56 at 6 weeks and 37.00 at 12 weeks [Figure - 2].
Mean reading speed showed a slight increase from 27.04 words/minute pretreatment to 34.52 words/minute at 4 weeks and 37.33 words/minute 12 weeks after TTT [Figure - 3].
Brief descriptions of two representative cases are given below.
Case 1: A 68-year-old lady presented with history of long-standing poor vision in the left eye and decreased vision in the right eye of 4 months' duration. Visual acuity was counting fingers close to face in the right eye and hand movements close to face in the left eye. Anterior segment examination was unremarkable except for the presence of early cataract in both eyes. Dilated pupil fundus examination revealed a disciform scar on the posterior pole of the left eye. In the right eye a large area of submacular exudation was seen [Figure - 4]a. Fundus fluorescein angiography [Figures 4]b and c revealed a large, predominantly occult CNVM in the right eye (~8-9 DD). The patient consented to TTT. Two spots of 3 mm size, power 450 mw were delivered using a volk quadraspheric lens, at the same sitting. At the four-week follow-up visit, her visual acuity improved to 1/60 (letter acuity 05) and FA showed a definitive reduction in the intensity of central hyperfluorescence.
Case 2: A 62-year-old non-smoking woman presented with sudden occurrence of metamorphopsia in the right eye of two-weeks' duration. She had undergone laser treatment (514 nm) for extrafoveal CNVM two years earlier. On examination, her visual acuity was 6/9 (letter acuity 75) in the left eye and 6/60 (letter acuity 35) in the right eye. Anterior segment examination was unremarkable in both eyes. Fundus examination of the left eye showed the presence of a large number of macular colloids. In the right eye there was a parafoveal pigmented scar, upper nasal to the centre of the fovea.
Fresh subretinal haemorrhage along with a grayish membrane was noted in the macular area involving the centre [Figure - 5]a. FA revealed a hypo fluorescent area with hyper fluorescence margin upper nasal to fovea, corresponding to the previous laser mark [Figures 5]b and c. Also evident was a well defined, predominantly classic subfoveal CNVM) and a circumlinear area of blocked fluorescence corresponding to the subretinal haemorrhage. She received a single sitting of TTT (3 mm spot size, 400 mw power for 60 sec) Twelve-week follow-up, the angiogram revealed disappearance of the subretinal haemorrhage and a partial resolution of subfoveal CNV. Her visual status stabilised (letter acuity 35) at 12 weeks after TTT.
| Discussion | | |
Visual loss due to subfoveal CNV secondary to AMD is a significant cause of posterior segment blindness in persons above 50 years of age and is presently not preventable. Several modes of therapy such as PDT, [5],[6],[7],[8]laser photocoagulation[17] and macular and submacular surgeries[13],[14],[15]have been used in an attempt to minimise collateral damage to the adjacent or overlying retina while treating subfoveal CNV.
PDT has undergone phase I, II and III trials showing an improvement of the visual acuity in 67% cases compared to placebo,[8] but it is not free of the side effects caused by the visudyne dye. The therapy is unfortunately expensive. Laser photocoagulation in subfoveal CNV secondary to AMD has several limitations. It is effective only in a small percentage (10-15%) of patients who have a well defined CNV with distinct margins; [17] there is likelihood of an immediate significant fall in the central vision with evolution of a dense central scotoma and finally there is higher rate of recurrence (35%). The visual results of submacular and macular surgeries in AMD have also not been very satisfactory. [13],[14],[15]These results nearly compare with the natural history of occult CNV in AMD, i.e., 63% suffer visual loss >3 lines over 6 months[18] and 41% suffer severe visual loss with in 12 months (decrease of
ž 6 lines).[17]
TTT is an upcoming mode of therapy for subfoveal CNV secondary to AMD, a fact also reflected in our study [Table - 1]. Reichel et al[9] in their initial study on 16 eyes of 15 patients reported an improvement of the visual acuity in 19% and stabilisation in 56% cases with no overt complications. They also reported a decrease in exudation in 94% of eyes up to an average of 11 months. Similarly, Newsom et al[10] reported closure of the membranes in 77% (34/44) of eyes with stabilisation of the visual acuity acuity in 47.7% (21/44) and improvement in 9% (4/44) up to an average of 6.1 months after TTT. Okada[19] reported improvement of the visual acuity in 5% (1/20), and stabilisation in 75% (15/20) with decreased exudation in 75% (15/20) eyes after a mean of 8.75 months after TTT [Table - 1].
In our study, visual acuity stabilised in 32% (16/50) and improved in 40% (20/50) eyes, whereas 28% (14/50) eyes showed a decrease of the vision at 3 months after TTT, the results being comparable to the earlier studies [Table - 1].
In addition to the visual acuity, we also recorded the scotoma score as well as reading speed before and after TTT, which have not been reported in the earlier studies. We found that the mean scotoma score decreased from 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.
The classic indications of TTT are occult CNV. In our set up, where PDT is either not easily available or is expensive, we did not differentiate between classic and occult CNV. Our sole criteria for inclusion in the present study were subfoveal CNV secondary to AMD. Though TTT has some advantages over other treatment modalities (PDT, Laser photocoagulation, etc.), its treatment variables have not been completely elucidated. The end point of no reaction or minimal colour change at the level of RPE, is difficult to determine clinically.
In the West, the standard power for 3mm spot size is 800-mW for 60 seconds [Table - 2]. But this power is too high for Indian pigmented eyes and certainly may lead to a retinal burn. From the present study experience, the suggested power to be used in Indian eyes is shown in Table 2; 400-550 mW power for a 3-mm spot size seems optimal. The power used may need to be adjusted according to variables such as age of patient, pigmentation, media clarity (phakic/pseudophakic), retinal oedema, haemorrhages, and location of CNV. Another crude method to calculate optimal power could be to put a test burn in the periphery, find the threshold and then reduce power by 10%.
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 importance of TTT as a treatment modality for sub-foveal CNVs especially in an Indian context. However, prospective, randomised 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 cheaper alternative to PDT, but also an efficacious tool in stabilisation or improvement of visual acuity.
| References | | |
| 1. | Macular Photocoagulation Study Group. Visual outcome after laser photocoagulation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Arch Ophthalmol 1994;112:480-88.  [ PUBMED] |
| 2. | Vingerling J, Dielemans I, Hoffman A, Grobbee DE, Hijmering M, Kramer CF, et al. The prevalence of age-related macular degeneration in the Rotterdam Study. Ophthalmology 1995;102:205-10. |
| 3. | Freund BK, Yannuzzi LA, Sorenson JA. Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol 1993;115:786-91. |
| 4. | Ferris III F, Fine S, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol 1984;102:1640-42. |
| 5. | Schmidt-Erfuth U, Miller J, Sickenberg M, Bunse A, Laqua H, Gragoudas E, et al. Photodynamic therapy of subfoveal choroidal neovascularization: clinical angiographic examples. Graefes Arch Clin Exp Ophthalmol 1998;236:365-74. |
| 6. | Schmidt-Erfuth U, Hasan T, Michaud N, Flotte TJ, Birngruber R. Vascular targeting in photodynamic occlusion of subretinal vessels. Ophthalmology 1994;101:153-61. |
| 7. | Miller J, Schmidt-Erfuth U, Sickenberg M. photodynamic therapy of subfoveal choroidal neovascularisation in age-related macular degeneration with verteporfin. Arch Ophthalmol 1999;117:1329-45. |
| 8. | Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin one-year results of 2 randomized clinical trials. TAP Report 1. Arch Ophthalmol 1999;117:1329-45. [ PUBMED] [ FULLTEXT] |
| 9. | Reichel E, Berrocal A, Ip M, Kroll AJ, Desai V, Dukar JS, et al. Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 1999;106:1908-14. |
| 10. | Newsom RSB, McAlister JC, Saeed M and McHugh JDA. Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularization. Br J Ophthalmol 2001;85:173-78. |
| 11. | Hart P, Chakravarthy U, MacKanzie G, Archer DB, Houston RF. Teletherapy for subfoveal choroidal neovascularization in age-related macular degeneration: results of follow-up in a nonrandomized study. Br J Ophthalmol 1998;80:1046-50. |
| 12. | Pharmacological Therapy for Macular Degeneration Study Group. Interferon alfa-2a in ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration: Results of a prospective randomized placebo-controlled clinical trial. Arch Ophthalmol 1997;115:865-72. [ PUBMED] |
| 13. | Fuzikado T, Ohji M, Hayashi A, Kusaka S, Tano Y. Anatomic and functional recovery of the fovea after foveal translocation surgery without large retinotomy and simultaneous excision of a neovascular membrane. Am J Ophthalmol 1998;126:839-42. |
| 14. | Wolf S, Lappas A, Weinberger A, et al. Macular translocation for surgical management of subfoveal choroidal neovascularizations in patients with AMD: First results. Graefes Arch Clin Exp Ophthalmol 1999;237:51-57. |
| 15. | Roth D, Downie A, Charles S. Visual results after submacular surgery for neovascularization in age-related macular degeneration. Ophthalmic Surg Lasers 1997;28: 920-25. |
| 16. | Eqert EM, Fine AM, Markowitz J, Maguire MG, Starr JS, Fine SL. Functional vision in patients with neovascular maculopathy and poor visual acuity. Arch Ophthalmol 1986;104:1009-12. |
| 17. | Bressler N, Frost L, Bressler S, Murphy RP, Fine SL. Natural course of poorly defined choroidal neovascularization associated with macular degeneration. Arch Ophthalmol 1988;106:1537-42. |
| 18. | Macular Photocoagulation Study Group. Occult choroidal neovascularization. Influence on visual outcome in patients with age-related macular degeneration. Arch Ophthalmol 1996;114:400-12. [ PUBMED] |
| 19. | Miller-Rivero NE, Kaplan HJ. Transpupillary thermotherapy in the treatment of occult and classic choroidal neovascularisation (Abstract). Invest Ophthalmol Vis Sci 2000;41:S179 |
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2]
| This article has been cited by | | 1 |
A pilot trial for comparison of photodynamic therapy and transpupillary thermotherapy for the management of classic subfoveal choroidal neovascularization secondary to age-related macular degeneration |
|
| Tewari, H.K., Prakash, G., Azad, R.V., Talwar, D., Kai, S. | | Indian Journal of Ophthalmology. 2007; 55(4): 277-281 | | [Pubmed] | | | 2 |
Transpupillary thermotherapy in the treatment of choroidal new vessels in age-related macular degeneration - One yearæs results | [Transpupilární termoterapie v léčbě choroidální neovaskularizace u věkem podmíně né makulární degenerace - Roční výsledky] |
|
| Studnička, J., Rencová, E., Korda, V., Hejcmanová, D., Dusová, J., Kvasnička, J. | | Ceska a Slovenska Oftalmologie. 2006; 62(3): 190-199 | | [Pubmed] | | | 3 |
Low vision aid in exudative macular degeneration treated by photodynamic therapy and thermal laser photocoagulation |
|
| Montero, J.A., Ruiz-Moreno, J.M., Sanchez de Castro, M.J., Fabiani, C. | | International Journal of Ophthalmology. 2006; 6(2): 298-301 | | [Pubmed] | | | 4 |
Evolution of retinal laser therapy: Minimum intensity photocoagulation (MIP). Can the laser heal the retina without harming it? |
|
| Dorin, G. | | Seminars in Ophthalmology. 2004; 19(1-2): 62-68 | | [Pubmed] | |
|
 |
|
|
|
Search Pubmed for