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Prophylactic Use of Apraclonidine for Intraocular Pressure Increase After Nd:YAG Capsulotomies
Vol. 114, No. 3
Correspondence
University, Osaka, Japan) and E13 (Biosoft, Paris, France), then stained with a three-step indirect immunoperoxidase method. Control procedures included the study of eye sections from an HIV-seronegative patient without retinitis, the use of respiratory syncytial virus anti body as an irrelevant monoclonal antibody, and immunoperoxidase staining in the absence of primary antibody. Positive control speci mens included human herpesvirus 6-infected lymphocytes, cytomegalovirus-infected human fibroblastic cells, and cytomegalovirus-infected brain tissue. Histologie examination of both eyes showed typical cytomegalic cells within the zones of retinal necrosis, and in the adjacent tissue. Cells positive for human herpesvirus 6 antigen were in the retina of the two patients and were mainly located in the ganglion cell layer (Fig ure, top). Some human herpesvirus 6-positive cells were also observed in the inner nuclear cell layer. Various human herpesvirus 6-specific staining aspects included cytoplasmic and nu clear small granulations or large inclusions (Figure, bottom); they could have been caused either by different stages of viral infection or by the different section levels. Cytomegalovirus antigens were detected on adjacent sections in the two cases. Our immunohistologic detection of human herpesvirus 6 in the retinas of patients with AIDS was unique; it was parallel to detection of cytomegalovirus. A crossreactivity of monoclo nal human herpesvirus 6 antibody has been excluded by a previous study 4 and other data (I.R., unpublished data, 1991). The human her pesvirus 6 and cytomegalovirus retinal coinfection in patients with AIDS and retinitis is thus authenticated. Human herpesvirus 6 could be an opportunistic agent leading to retinitis dur ing AIDS. The in vitro sensitivity of human herpesvirus 6 to available antiviral agents 6 re quires that the potential opportunistic role, especially in the retina, be explored. Currently, a study is being undertaken to correlate clinical data and results obtained by immunohistochemical analysis, in situ hybridization, and polymerase chain reaction.
References 1. Salahuddin, S. Z., Ablashi, D. V., Markham, P. D., Josephs, S. F., Sturzenzgger, S., Kaplan, M.,
377
Halligan, G., Biberfeld, P., Wong-Staal, F., Kramarsky, B., and Gallo, R. C: Isolation of a new virus, HBLV, in patients with lymphoproliferative disor ders. Science 234:596, 1986. 2. Carrigan, D. R., Drobyski, W. R., Russler, S. K., Tapper, M. A., Knox, K. K., and Ash, R. C : Intersti tial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation. Lancet 338:147, 1991. 3. Qavi, H. B., Green, M. T., SeGall, G. K., and Font, R. L.: Demonstration of HIV-1 and HHV-6 in AIDS-associated retinitis. Curr. Eye Res. 8:379, 1989. 4. Okuno, T., Higashi, K., and Shiraki, K.: Human herpesvirus 6 infection in renal transplantation. Transplantation 49:519, 1990. 5. Agut, H., Collandre, H„ Aubin, J.-T., Guetard, D., Favier, V., Ingrand, D., Montagnier, L., and Huraux, J.-M.: In vitro sensitivity of human herpesvirus-6 to antiviral drugs. Res. Virol. 140:219, 1989.
Correspondence Correspondence concerning recent articles or other mate rial published in THE JOURNAL should be submitted within six weeks of publication. Correspondence must be typed double-spaced, on 8¢ x 11-inch bond paper with lVHnch margins on all four sides and should be no more than two typewritten pages in length. Every effort will be made to resolve controversies between the correspondents and the authors of the article before publication.
Prophylactic Use of Apraclonidine for Intraocular Pressure Increase After Nd:YAG Capsulotomies EDITOR: In the article, "Prophylactic use of apraclo nidine for intraocular pressure increase after Nd:YAG capsulotomies," by D. E. Silverstone, S. F. Brint, K. W. Olander, R. B. Taylor, G. R. McCarty, j . M. deFaller, and L. L. Burk (Am. J. Ophthalmol. 113:401, April 1992), the authors showed apraclonidine to be effective in attenu ating the incidence of severity of increases in intraocular pressure in the first three hours af ter the treatment. However, I have several clin ical cases to illustrate the need to use caution in concluding the lack of a deleterious pres sure increase if one considers only the imme diate postoperative hours. I treated three pa tients with apraclonidine before a YAG
378
AMERICAN JOURNAL OF OPHTHALMOLOGY
capsulotomy. Subsequent pressure checks at two to three hours were unremarkable. How ever, each of these three patients had a marked increase on a pressure determination at 24 hours. These patients all had previous uncomplicat ed extracapsular extractions with posterior chamber lens implantation. The preoperative pressures were 10, 20, and 22 mm Hg, respec tively. The last patient, suspected of having glaucoma, had a normal optic nerve and visual field. One drop of apraclonidine was given to each patient 20 to 30 minutes before the pro cedure was performed. One drop of prednisolone acetate was given postoperatively and continued three times a day for one week. Pressures were checked two to three hours af ter the laser procedure and again at 24 hours. To achieve a central capsulotomy in each of these three patients, 34, 13, and 17 mj were used, respectively. The pressures at three hours were 13, 20, and 21 mm Hg, respec tively. On the first postoperative day these patients had a marked visual improvement with com fortable eyes, an anterior chamber reaction of trace to mild cells, and pressures of 43, 50, and 49 mm Hg, respectively. Gonioscopy per formed on the first two patients disclosed widely open aphakic angles. The pressures re sponded in each patient to topical betablockers and carbonic anhydrase inhibitors. Pressures were controlled within several hours to levels between 20 and 22 mm Hg. All pa tients have subsequently done well and did not require medications after the first week. The course of these patients indicates that one may get a false sense of reassurance that an intraocular pressure spike has not occurred after a YAG capsulotomy if one only checks the pressure several hours after treatment. If one is concerned about the deleterious effects of a pressure increase, then it would appear that a determination at 24 hours would be helpful in identifying those few patient in whom the protective effect of apraclonidine in transitory. ANDREW ROMANOWSKI, M.D.
Portland, Oregon
Reply EDITOR:
We appreciate Dr. Romanowski's response to our article. Dr. Romanowski relates his experi ence with three patients in whom there was
September, 1992
significant increase in intraocular pressure one day, but not three hours after Nd:YAG laser capsulotomy. We concur with Dr. Romanow ski's point that there may be patients who demonstrate no significant pressure increase within the first several hours after laser treat ment who may have increases one day later. Several factors were considered in the design of our study. There were reports that the maxi mal mean postlaser increase in intraocular pressure occurred during the first several hours after the procedure.1"3 In a study conducted by one of us, 3 incidence of pressure increases (2: 10 mm Hg) within the first several hours after capsulotomy was 38% (eight of 21 pa tients). At 24 hours it was 0% (none of 20 patients). 3 In a report of 32 patients, all of the eyes with an increased pressure at 24 hours above baseline also had an increase within the first several hours. 2 In another study of 37 capsulotomies, none of the patients with a pres sure increase less than 5 mm Hg during the first four hours after capsulotomy had an in crease above 10 mm Hg at a later time. 1 The maximal ocular hypotensive effect of apraclonidine occurs within two to five hours after installation, with effects lasting at least 12 hours. 4 · 5 Thus, the time-course of the treat ment and of the condition seemed to be a good match. Concerning the medication regimen used by Dr. Romanowski, one drop of apraclonidine was instilled 20 to 30 minutes before laser treatment. In our study, we instilled two drops of apraclonidine, which is consistent with the currently approved product labeling: one drop one hour before the procedure and one drop immediately afterward. It is interesting to note reports that apraclonidine, when used in con junction with cataract extraction, is not effec tive unless dosed one hour preoperatively. 7,8 Dr. Romanowski also used prednisolone ace tate, three times a day, for one week after laser treatment, whereas we did not. An increased pressure within one day after start of corticosteroid therapy is early for a classic corticosteroid-responder glaucoma. Nevertheless, it is difficult to assess its role in these cases. We reported that prophylactic use of apra clonidine decreased the incidence of increases in intraocular pressure after laser treatment. We did not, however, intend readers to infer that such treatment provides an abolition of these increases at all times in all patients. The significance of Dr. Romanowski's deviation from label protocol is also not assessed here. In addition to the cases provided by Dr. Roman-
Correspondence
University, Osaka, Japan) and E13 (Biosoft, Paris, France), then stained with a three-step indirect immunoperoxidase method. Control procedures included the study of eye sections from an HIV-seronegative patient without retinitis, the use of respiratory syncytial virus anti body as an irrelevant monoclonal antibody, and immunoperoxidase staining in the absence of primary antibody. Positive control speci mens included human herpesvirus 6-infected lymphocytes, cytomegalovirus-infected human fibroblastic cells, and cytomegalovirus-infected brain tissue. Histologie examination of both eyes showed typical cytomegalic cells within the zones of retinal necrosis, and in the adjacent tissue. Cells positive for human herpesvirus 6 antigen were in the retina of the two patients and were mainly located in the ganglion cell layer (Fig ure, top). Some human herpesvirus 6-positive cells were also observed in the inner nuclear cell layer. Various human herpesvirus 6-specific staining aspects included cytoplasmic and nu clear small granulations or large inclusions (Figure, bottom); they could have been caused either by different stages of viral infection or by the different section levels. Cytomegalovirus antigens were detected on adjacent sections in the two cases. Our immunohistologic detection of human herpesvirus 6 in the retinas of patients with AIDS was unique; it was parallel to detection of cytomegalovirus. A crossreactivity of monoclo nal human herpesvirus 6 antibody has been excluded by a previous study 4 and other data (I.R., unpublished data, 1991). The human her pesvirus 6 and cytomegalovirus retinal coinfection in patients with AIDS and retinitis is thus authenticated. Human herpesvirus 6 could be an opportunistic agent leading to retinitis dur ing AIDS. The in vitro sensitivity of human herpesvirus 6 to available antiviral agents 6 re quires that the potential opportunistic role, especially in the retina, be explored. Currently, a study is being undertaken to correlate clinical data and results obtained by immunohistochemical analysis, in situ hybridization, and polymerase chain reaction.
References 1. Salahuddin, S. Z., Ablashi, D. V., Markham, P. D., Josephs, S. F., Sturzenzgger, S., Kaplan, M.,
377
Halligan, G., Biberfeld, P., Wong-Staal, F., Kramarsky, B., and Gallo, R. C: Isolation of a new virus, HBLV, in patients with lymphoproliferative disor ders. Science 234:596, 1986. 2. Carrigan, D. R., Drobyski, W. R., Russler, S. K., Tapper, M. A., Knox, K. K., and Ash, R. C : Intersti tial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation. Lancet 338:147, 1991. 3. Qavi, H. B., Green, M. T., SeGall, G. K., and Font, R. L.: Demonstration of HIV-1 and HHV-6 in AIDS-associated retinitis. Curr. Eye Res. 8:379, 1989. 4. Okuno, T., Higashi, K., and Shiraki, K.: Human herpesvirus 6 infection in renal transplantation. Transplantation 49:519, 1990. 5. Agut, H., Collandre, H„ Aubin, J.-T., Guetard, D., Favier, V., Ingrand, D., Montagnier, L., and Huraux, J.-M.: In vitro sensitivity of human herpesvirus-6 to antiviral drugs. Res. Virol. 140:219, 1989.
Correspondence Correspondence concerning recent articles or other mate rial published in THE JOURNAL should be submitted within six weeks of publication. Correspondence must be typed double-spaced, on 8¢ x 11-inch bond paper with lVHnch margins on all four sides and should be no more than two typewritten pages in length. Every effort will be made to resolve controversies between the correspondents and the authors of the article before publication.
Prophylactic Use of Apraclonidine for Intraocular Pressure Increase After Nd:YAG Capsulotomies EDITOR: In the article, "Prophylactic use of apraclo nidine for intraocular pressure increase after Nd:YAG capsulotomies," by D. E. Silverstone, S. F. Brint, K. W. Olander, R. B. Taylor, G. R. McCarty, j . M. deFaller, and L. L. Burk (Am. J. Ophthalmol. 113:401, April 1992), the authors showed apraclonidine to be effective in attenu ating the incidence of severity of increases in intraocular pressure in the first three hours af ter the treatment. However, I have several clin ical cases to illustrate the need to use caution in concluding the lack of a deleterious pres sure increase if one considers only the imme diate postoperative hours. I treated three pa tients with apraclonidine before a YAG
378
AMERICAN JOURNAL OF OPHTHALMOLOGY
capsulotomy. Subsequent pressure checks at two to three hours were unremarkable. How ever, each of these three patients had a marked increase on a pressure determination at 24 hours. These patients all had previous uncomplicat ed extracapsular extractions with posterior chamber lens implantation. The preoperative pressures were 10, 20, and 22 mm Hg, respec tively. The last patient, suspected of having glaucoma, had a normal optic nerve and visual field. One drop of apraclonidine was given to each patient 20 to 30 minutes before the pro cedure was performed. One drop of prednisolone acetate was given postoperatively and continued three times a day for one week. Pressures were checked two to three hours af ter the laser procedure and again at 24 hours. To achieve a central capsulotomy in each of these three patients, 34, 13, and 17 mj were used, respectively. The pressures at three hours were 13, 20, and 21 mm Hg, respec tively. On the first postoperative day these patients had a marked visual improvement with com fortable eyes, an anterior chamber reaction of trace to mild cells, and pressures of 43, 50, and 49 mm Hg, respectively. Gonioscopy per formed on the first two patients disclosed widely open aphakic angles. The pressures re sponded in each patient to topical betablockers and carbonic anhydrase inhibitors. Pressures were controlled within several hours to levels between 20 and 22 mm Hg. All pa tients have subsequently done well and did not require medications after the first week. The course of these patients indicates that one may get a false sense of reassurance that an intraocular pressure spike has not occurred after a YAG capsulotomy if one only checks the pressure several hours after treatment. If one is concerned about the deleterious effects of a pressure increase, then it would appear that a determination at 24 hours would be helpful in identifying those few patient in whom the protective effect of apraclonidine in transitory. ANDREW ROMANOWSKI, M.D.
Portland, Oregon
Reply EDITOR:
We appreciate Dr. Romanowski's response to our article. Dr. Romanowski relates his experi ence with three patients in whom there was
September, 1992
significant increase in intraocular pressure one day, but not three hours after Nd:YAG laser capsulotomy. We concur with Dr. Romanow ski's point that there may be patients who demonstrate no significant pressure increase within the first several hours after laser treat ment who may have increases one day later. Several factors were considered in the design of our study. There were reports that the maxi mal mean postlaser increase in intraocular pressure occurred during the first several hours after the procedure.1"3 In a study conducted by one of us, 3 incidence of pressure increases (2: 10 mm Hg) within the first several hours after capsulotomy was 38% (eight of 21 pa tients). At 24 hours it was 0% (none of 20 patients). 3 In a report of 32 patients, all of the eyes with an increased pressure at 24 hours above baseline also had an increase within the first several hours. 2 In another study of 37 capsulotomies, none of the patients with a pres sure increase less than 5 mm Hg during the first four hours after capsulotomy had an in crease above 10 mm Hg at a later time. 1 The maximal ocular hypotensive effect of apraclonidine occurs within two to five hours after installation, with effects lasting at least 12 hours. 4 · 5 Thus, the time-course of the treat ment and of the condition seemed to be a good match. Concerning the medication regimen used by Dr. Romanowski, one drop of apraclonidine was instilled 20 to 30 minutes before laser treatment. In our study, we instilled two drops of apraclonidine, which is consistent with the currently approved product labeling: one drop one hour before the procedure and one drop immediately afterward. It is interesting to note reports that apraclonidine, when used in con junction with cataract extraction, is not effec tive unless dosed one hour preoperatively. 7,8 Dr. Romanowski also used prednisolone ace tate, three times a day, for one week after laser treatment, whereas we did not. An increased pressure within one day after start of corticosteroid therapy is early for a classic corticosteroid-responder glaucoma. Nevertheless, it is difficult to assess its role in these cases. We reported that prophylactic use of apra clonidine decreased the incidence of increases in intraocular pressure after laser treatment. We did not, however, intend readers to infer that such treatment provides an abolition of these increases at all times in all patients. The significance of Dr. Romanowski's deviation from label protocol is also not assessed here. In addition to the cases provided by Dr. Roman-