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Thermotherapy of occult subfoveal choroidal neovascularization
Letters to the Editor 8. McPherson SD, Jr. Discussion. Trans Am Ophthalmol Soc 1963;61:178 –9.
Author’s reply Dear Editor: In my discussion of the article, “Fluid Lamellar Keratoplasty in Keratoconus” by Amayem and Anwar, I mentioned that Dr. Malbran did not include visual results in his report “Lamellar Keratoplasty in Corneal Ectasias” in 1972. This was incorrect; he did include visual results in 70 of his 115 cases. On page 62, Dr. Malbran states “We are able to report that of the 115 eyes operated by us so far, in not one of them has the final result been worse than the preoperative condition.” In the next paragraph he states, “In the 70 cases analyzed by us, a greater or lesser functional improvement was obtained as compared with the initial condition.” Dr. Malbran stated that in not 1 of all 115 cases was the final result worse than the preoperative condition; however, he only analyzes 70 cases. It would have been helpful for him to state what the length of time was after surgery that the analysis occurred. At what specific intervals were the 45 cases that were not analyzed lost to follow up. Understandably, this article was published in 1972, and it is impossible to retrieve this information now. Dr. Malbran is to be congratulated for his pioneering work in this field, which is bearing more fruit almost 30 years later. PETER R. LAIBSON, MD Philadelphia, Pennsylvania
Sterilization by Plasma Gas Dear Editor: The article by Smith et al1 is most important. Toxins strong enough to sterilize are also capable of destroying cells inside the eye. To the possible causes of idiopathic postoperative corneal edema listed by Dr. MacRae in his Discussion, I would add, from experience: distilled water. Some years ago, when solutions were still supplied to the surgeon by pouring from a stock bottle into a small dish or glass, I had the misfortune to see a cornea turn gradually cloudy by the end of a very smooth cataract extraction. Checking with the operating room staff yielded no clues, and I assumed I had done something wrong, but when the next case did the same thing, I halted surgery and made a thorough investigation. It turned out that a new circulating nurse had given me distilled water for irrigation of the anterior chamber. Fortunately, both corneas cleared within 48 hours, and the patients did well for the 10⫹ years that I followed them. (Endothelial cells counts were not possible back then.) Although such an incident would not occur in our operating rooms today, the warning remains prudent for two reasons: (1) Not all operating rooms worldwide have our luxuries; (2) From time to time I hear a proposal for the use of distilled water to destroy residual lens epithelial cells at the end of cataract surgery to prevent secondary cataract. ROBERT C. DREWS, MD St. Louis, Missouri
Reference 1. Smith CA, Khoury JM, Shields SM, et al. Unexpected corneal endothelial cell decompensation after intraocular surgery with instruments sterilized by plasma gas. Ophthalmology 2000;107: 1561– 6; discussion 1567.
Thermotherapy of Occult Subfoveal Choroidal Neovascularization Dear Editor: In the article by Reichel, et al, “Transpupillary Thermotherapy of Occult Subfoveal Choroidal Neovascularization in Patients with Age-related Macular Degeneration” (Ophthalmology 1999;106:1908 –14), the authors report the results of a pilot study on 16 eyes with occult subfoveal choroidal neovascularization (CNV) treated with near-infrared diode (810 nm) thermotherapy. The treatment was conducted with a large spot (1.2, 2.0, and 3.0 mm) and an exposure time of 60 seconds. In contrast to suprathreshold standard laser irradiation, the end point of transpupillary thermotherapy (TTT) was not tissue coagulation but a controlled, gradual rise of temperature above 45 °C at the level of the lesion. In general, no or minimal retinal color was obtained during laser exposure. During TTT with the infrared wavelength, retinal pigment epithelium (RPE) and choroidal melanocytes are the sole target, because oxyhemoglobin or reduced hemoglobin do not absorb the radiation at low energies.1 In almost all cases decreased exudation was achieved. Three eyes (19%) showed an improvement in visual acuity, and in nine eyes (56%) visual acuity remained stable. These are encouraging results, and the authors are to be commended for exploring new modalities of therapeutic laser irradiation of the choroid and retina. The study by Reichel, et al raises an important question with respect to the mechanisms responsible for the “closure” of CNV. After more than 30 years of application of laser thermal photocoagulation in ophthalmology, most of the therapeutic mechanisms related to the procedure are still under debate. This uncertainty is particularly evident for TTT, a technique inherited from oncology. In the cases treated by Reichel, et al, some observations are quite interesting and need further discussion: (1) Decreased exudation was obtained in almost all the eyes despite a surprisingly low number of treatments. Thirteen eyes received only one treatment during a mean follow-up time of 12 months. (2) At the end of follow-up, all cases studied with fluorescein angiography (10 of 16) showed some hyperfluorescence of the lesion that was attributed to “late staining of subretinal fibrosis.” It is likely that TTT does not ablate neovascularization but rather slows its progression. This can be obtained with only one application of laser hyperthermia in most patients with the occult form of CNV. Miller, et al showed that after laser irradiation, the neovascular lesion may become enveloped by multiple layers of RPE fibrous tissue, and this complex limits continued growth of the neovascular lesion and therefore limits the extent of the retina that otherwise would be damaged by the natural course of the disease. RPE proliferation may play a role in treating CNV by enveloping the lesion and absorbing the fluid that separates the neovascularization from the overlying sensory
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Ophthalmology Volume 108, Number 6, June 2001 retina.2 The beneficial effect of factors derived from a “stimulated” RPE, such as transforming growth factor-1 and transforming growth factor-2, should also be considered (Invest Ophthalmol Vis Sci 1997;38[Suppl]:754). Suprathreshold laser photocoagulation is the standard treatment for CNV but is associated with diffuse retinal damage. The current visible end point (i.e., retinal whitening) during laser photocoagulation results in a coagulative necrosis of the whole retina, with nonspecific targeting of cells caused by extensive diffusion of thermal energy. This damage may not be needed for the therapeutic effects. PAOLO LANZETTA, MD PAOLA MICHIELETTO, MD Udine, Italy References 1. Lanzetta P, Virgili G, Ferrari E, Menchini U. Diode laser photocoagulation of choroidal neovascular membranes. Int Ophthalmol 1996;19:347–54. 2. Miller H, Miller B, Ryan SJ. The role of retinal pigment epithelium in the involution of subretinal neovascularization. Invest Ophthalmol Vis Sci 1986;27:1644 –52.
Author’s reply Dear Editor: Drs. Lanzetta and Michieletto raise interesting questions regarding the pathophysiology of transpupillary thermotherapy’s (TTT) effect on choroidal neovascularization (CNV).1 Modulation of neovascular stimuli appears to be critical in the treatment of many retinal (e.g., diabetic retinopathy) and choroidal neovascular disorders. TTT may be more effective in closing CNV in that suprathreshold laser may actually increase those factors that stimulate inflammation, and this ultimately may be responsible for further induction of angiogenesis. This may explain the high recurrence rate observed after conventional suprathreshold laser treatment of CNV. Thermal obliteration of abnormal vessels and retinal pigment epithelium migration, transformation, and proliferation are mechanisms of CNV closure that TTT (long-pulse photocoagulation) may share with conventional short-pulse laser photocoagulation. TTT or long-pulse photocoagulation may differ in that this modality of treatment may cause thrombosis, thermal inhibition of angiogenesis, or neovascular apoptosis. TTT requires a large treatment area, and this may help modulate neovascular stimuli as well. TTT
represents a paradigm shift, for the laser photocoagulation on CNV, in that less may be more. ELIAS REICHEL, MD Boston, Massachusetts Reference 1. Reichel E, Berrocal AM, Ip M, et al. Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 1999;106:1908 –14.
Allvar Gullstrand Dear Editor: The historical image of Allvar Gullstrand, MD (1862–1930) in the September 2000 issue states he is the only ophthalmologist who has received a Nobel Prize.1 Gullstrand was the awardee in physiology or medicine in 1911. Ophthalmologists should be proud to know that the list of their colleagues who have received this illustrious award is longer.2 Fritz Pregl, MD (1869 –1930), an Austrian ophthalmologist and analytical chemist, received the Nobel Prize in chemistry in 1923. Walter Hess, MD (1881–1973), a Swiss ophthalmologist and physiologist, was awarded the Nobel Prize in physiology or medicine in 1949 for his work on autonomic control by the hypothalamus. JAMES G. RAVIN, MD Toledo, Ohio References 1. Kearney J, Tanaka S. Historical image. Ophthalmology 2000; 107:1680. 2. Ravin JG. Gullstrand, Einstein, and the Nobel Prize. Arch Ophthalmol 1999;117:670 –2.
Author’s reply Dear Editor: We thank Dr. Ravin for his interest in our article and for pointing out the often repeated error that Dr. Gullstrand was the only ophthalmologist to have received a Nobel Prize. We noted in Dr. Ravin’s article (Arch Ophthalmol 1999; 117:670 –2) and in his presentation at the Academy’s Annual Meeting (October 24, 1999), that other ophthalmologists had received the Prize but were not engaged actively in the practice of ophthalmology. We regret not having made that fine distinction. JOHN J. KEARNEY, MD STEPHEN C. TANAKA, MD Hayward, California
Errata Paul Sternberg, Jr., MD, of Atlanta, Georgia, should have been listed as an author of the March 2001 Guest Editorial, “Are the Submacular Surgery Trials Still Relevant in an Era of Photodynamic Therapy?” Dr. Sternberg’s name was inadvertently misspelled, and we apologize for any inconvenience this may have caused.
The correct title of the article by Levartovsky S, Rosenwasser GOD, Goodman DF (Ophthalmology 2001;108:321–5) is “Bacterial Keratitis after Laser In Situ Keratomileusis.” The error is regretted.
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Author’s reply Dear Editor: In my discussion of the article, “Fluid Lamellar Keratoplasty in Keratoconus” by Amayem and Anwar, I mentioned that Dr. Malbran did not include visual results in his report “Lamellar Keratoplasty in Corneal Ectasias” in 1972. This was incorrect; he did include visual results in 70 of his 115 cases. On page 62, Dr. Malbran states “We are able to report that of the 115 eyes operated by us so far, in not one of them has the final result been worse than the preoperative condition.” In the next paragraph he states, “In the 70 cases analyzed by us, a greater or lesser functional improvement was obtained as compared with the initial condition.” Dr. Malbran stated that in not 1 of all 115 cases was the final result worse than the preoperative condition; however, he only analyzes 70 cases. It would have been helpful for him to state what the length of time was after surgery that the analysis occurred. At what specific intervals were the 45 cases that were not analyzed lost to follow up. Understandably, this article was published in 1972, and it is impossible to retrieve this information now. Dr. Malbran is to be congratulated for his pioneering work in this field, which is bearing more fruit almost 30 years later. PETER R. LAIBSON, MD Philadelphia, Pennsylvania
Sterilization by Plasma Gas Dear Editor: The article by Smith et al1 is most important. Toxins strong enough to sterilize are also capable of destroying cells inside the eye. To the possible causes of idiopathic postoperative corneal edema listed by Dr. MacRae in his Discussion, I would add, from experience: distilled water. Some years ago, when solutions were still supplied to the surgeon by pouring from a stock bottle into a small dish or glass, I had the misfortune to see a cornea turn gradually cloudy by the end of a very smooth cataract extraction. Checking with the operating room staff yielded no clues, and I assumed I had done something wrong, but when the next case did the same thing, I halted surgery and made a thorough investigation. It turned out that a new circulating nurse had given me distilled water for irrigation of the anterior chamber. Fortunately, both corneas cleared within 48 hours, and the patients did well for the 10⫹ years that I followed them. (Endothelial cells counts were not possible back then.) Although such an incident would not occur in our operating rooms today, the warning remains prudent for two reasons: (1) Not all operating rooms worldwide have our luxuries; (2) From time to time I hear a proposal for the use of distilled water to destroy residual lens epithelial cells at the end of cataract surgery to prevent secondary cataract. ROBERT C. DREWS, MD St. Louis, Missouri
Reference 1. Smith CA, Khoury JM, Shields SM, et al. Unexpected corneal endothelial cell decompensation after intraocular surgery with instruments sterilized by plasma gas. Ophthalmology 2000;107: 1561– 6; discussion 1567.
Thermotherapy of Occult Subfoveal Choroidal Neovascularization Dear Editor: In the article by Reichel, et al, “Transpupillary Thermotherapy of Occult Subfoveal Choroidal Neovascularization in Patients with Age-related Macular Degeneration” (Ophthalmology 1999;106:1908 –14), the authors report the results of a pilot study on 16 eyes with occult subfoveal choroidal neovascularization (CNV) treated with near-infrared diode (810 nm) thermotherapy. The treatment was conducted with a large spot (1.2, 2.0, and 3.0 mm) and an exposure time of 60 seconds. In contrast to suprathreshold standard laser irradiation, the end point of transpupillary thermotherapy (TTT) was not tissue coagulation but a controlled, gradual rise of temperature above 45 °C at the level of the lesion. In general, no or minimal retinal color was obtained during laser exposure. During TTT with the infrared wavelength, retinal pigment epithelium (RPE) and choroidal melanocytes are the sole target, because oxyhemoglobin or reduced hemoglobin do not absorb the radiation at low energies.1 In almost all cases decreased exudation was achieved. Three eyes (19%) showed an improvement in visual acuity, and in nine eyes (56%) visual acuity remained stable. These are encouraging results, and the authors are to be commended for exploring new modalities of therapeutic laser irradiation of the choroid and retina. The study by Reichel, et al raises an important question with respect to the mechanisms responsible for the “closure” of CNV. After more than 30 years of application of laser thermal photocoagulation in ophthalmology, most of the therapeutic mechanisms related to the procedure are still under debate. This uncertainty is particularly evident for TTT, a technique inherited from oncology. In the cases treated by Reichel, et al, some observations are quite interesting and need further discussion: (1) Decreased exudation was obtained in almost all the eyes despite a surprisingly low number of treatments. Thirteen eyes received only one treatment during a mean follow-up time of 12 months. (2) At the end of follow-up, all cases studied with fluorescein angiography (10 of 16) showed some hyperfluorescence of the lesion that was attributed to “late staining of subretinal fibrosis.” It is likely that TTT does not ablate neovascularization but rather slows its progression. This can be obtained with only one application of laser hyperthermia in most patients with the occult form of CNV. Miller, et al showed that after laser irradiation, the neovascular lesion may become enveloped by multiple layers of RPE fibrous tissue, and this complex limits continued growth of the neovascular lesion and therefore limits the extent of the retina that otherwise would be damaged by the natural course of the disease. RPE proliferation may play a role in treating CNV by enveloping the lesion and absorbing the fluid that separates the neovascularization from the overlying sensory
1011
Ophthalmology Volume 108, Number 6, June 2001 retina.2 The beneficial effect of factors derived from a “stimulated” RPE, such as transforming growth factor-1 and transforming growth factor-2, should also be considered (Invest Ophthalmol Vis Sci 1997;38[Suppl]:754). Suprathreshold laser photocoagulation is the standard treatment for CNV but is associated with diffuse retinal damage. The current visible end point (i.e., retinal whitening) during laser photocoagulation results in a coagulative necrosis of the whole retina, with nonspecific targeting of cells caused by extensive diffusion of thermal energy. This damage may not be needed for the therapeutic effects. PAOLO LANZETTA, MD PAOLA MICHIELETTO, MD Udine, Italy References 1. Lanzetta P, Virgili G, Ferrari E, Menchini U. Diode laser photocoagulation of choroidal neovascular membranes. Int Ophthalmol 1996;19:347–54. 2. Miller H, Miller B, Ryan SJ. The role of retinal pigment epithelium in the involution of subretinal neovascularization. Invest Ophthalmol Vis Sci 1986;27:1644 –52.
Author’s reply Dear Editor: Drs. Lanzetta and Michieletto raise interesting questions regarding the pathophysiology of transpupillary thermotherapy’s (TTT) effect on choroidal neovascularization (CNV).1 Modulation of neovascular stimuli appears to be critical in the treatment of many retinal (e.g., diabetic retinopathy) and choroidal neovascular disorders. TTT may be more effective in closing CNV in that suprathreshold laser may actually increase those factors that stimulate inflammation, and this ultimately may be responsible for further induction of angiogenesis. This may explain the high recurrence rate observed after conventional suprathreshold laser treatment of CNV. Thermal obliteration of abnormal vessels and retinal pigment epithelium migration, transformation, and proliferation are mechanisms of CNV closure that TTT (long-pulse photocoagulation) may share with conventional short-pulse laser photocoagulation. TTT or long-pulse photocoagulation may differ in that this modality of treatment may cause thrombosis, thermal inhibition of angiogenesis, or neovascular apoptosis. TTT requires a large treatment area, and this may help modulate neovascular stimuli as well. TTT
represents a paradigm shift, for the laser photocoagulation on CNV, in that less may be more. ELIAS REICHEL, MD Boston, Massachusetts Reference 1. Reichel E, Berrocal AM, Ip M, et al. Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 1999;106:1908 –14.
Allvar Gullstrand Dear Editor: The historical image of Allvar Gullstrand, MD (1862–1930) in the September 2000 issue states he is the only ophthalmologist who has received a Nobel Prize.1 Gullstrand was the awardee in physiology or medicine in 1911. Ophthalmologists should be proud to know that the list of their colleagues who have received this illustrious award is longer.2 Fritz Pregl, MD (1869 –1930), an Austrian ophthalmologist and analytical chemist, received the Nobel Prize in chemistry in 1923. Walter Hess, MD (1881–1973), a Swiss ophthalmologist and physiologist, was awarded the Nobel Prize in physiology or medicine in 1949 for his work on autonomic control by the hypothalamus. JAMES G. RAVIN, MD Toledo, Ohio References 1. Kearney J, Tanaka S. Historical image. Ophthalmology 2000; 107:1680. 2. Ravin JG. Gullstrand, Einstein, and the Nobel Prize. Arch Ophthalmol 1999;117:670 –2.
Author’s reply Dear Editor: We thank Dr. Ravin for his interest in our article and for pointing out the often repeated error that Dr. Gullstrand was the only ophthalmologist to have received a Nobel Prize. We noted in Dr. Ravin’s article (Arch Ophthalmol 1999; 117:670 –2) and in his presentation at the Academy’s Annual Meeting (October 24, 1999), that other ophthalmologists had received the Prize but were not engaged actively in the practice of ophthalmology. We regret not having made that fine distinction. JOHN J. KEARNEY, MD STEPHEN C. TANAKA, MD Hayward, California
Errata Paul Sternberg, Jr., MD, of Atlanta, Georgia, should have been listed as an author of the March 2001 Guest Editorial, “Are the Submacular Surgery Trials Still Relevant in an Era of Photodynamic Therapy?” Dr. Sternberg’s name was inadvertently misspelled, and we apologize for any inconvenience this may have caused.
The correct title of the article by Levartovsky S, Rosenwasser GOD, Goodman DF (Ophthalmology 2001;108:321–5) is “Bacterial Keratitis after Laser In Situ Keratomileusis.” The error is regretted.
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