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Risk Factors for the Development of Rhegmatogenous Retinal Detachment in Patients With Cytomegalovirus Retinitis: Reply
Vol. 118, No. 5
ment of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis," by W. R. Freeman, D. N. Friedberg, C. Berry, j . I. Quiceno, M. Behette, S. C. Fullerton, and D. Munguia (Am. J. Ophthalmol. 116:713, De cember 1993), the authors observed that reti nal detachment complicating cytomegalovirus retinitis occurred more frequently when 25% or more of the peripheral retina was involved and when the retinitis was poorly controlled. Our current treatment of cytomegalovirus reti nitis has resulted in few retinal detachments and little loss of vision. We have achieved this by early detection through screening, 1 effective control of the retinitis, 2 and treating those most at risk of retinal detachment with prophylatic laser. We currently screen all AIDS outpatients who have a CD4 count of 0.05 x 109/1 or less every three months. We also screen AIDS pa tients admitted to the hospital for any AIDSrelated illness. Over the last two years we have screened over 270 patients and found 15 (23 eyes) with cytomegalovirus retinitis; five of those patients were asymptomatic at diagnosis. In all, 39 patients were treated for more than six weeks, 22 (35 eyes) with high-dose intravit real ganciclovir and four (seven eyes) with in travenous ganciclovir. The posterior pole was affected in nine eyes, peripheral retina in 23, and both regions in seven. Using high-dose intravitreal ganciclovir (2 mg/0.1 ml), we were able to achieve 100% resolution of the retinitis, with relapse occur ring at a median of 42 weeks in only two pa tients on weekly maintainance intravitreal in jections. The reactivation of the retinitis settled with therapy of two injections a week for three weeks. Of the four patients treated with intravenous ganciclovir, relapse occurred in three within eight weeks. For those patients who had more than 25% of the peripheral retina involved, we adminis tered laser photocoagulation as a band entrap ping the region involved. Using an argon laser and panfundoscope or three-mirror lens, we placed burns three or four deep, one spot apart, to give a full-thickness burn. Nine eyes received prophylactic laser, three of which went on to retinal detachment that was con tained by the band of laser, and visual acuity was not affected. Two patients had retinal detachments requir ing surgery. One had a small area of retinitis and responded well to a scierai buckle proce dure and intravitreal therapy. The other had extensive bilateral disease with subretinal fluid
Correspondence
685
detaching both maculae. He did poorly despite vitrectomy, silicone oil replacement, and intra venous foscarnet, never achieving good control of the retinitis or vision better than counting fingers. We look forward to a clinical trial confirming our clinical impression that early effective treatment, and prophylatic laser therapy will reduce the 25% incidence of retinal detach ment in cytomegalovirus retinitis. NIGEL MORLET, M.B., F.R.A.C.O. STEPHANIE YOUNG, M.B., F.R.A.C.O. MINAS T. CORNEO, M.S., F.R.A.C.O. Randwick, New South Wales, Australia
References 1. Morlet N, Young SR, Dean R, Gold J. Ophthalmological screening for CMV retinitis in HIV infection. Lancet 1992;340:179. 2. Young SR, Morlet N, Heery S, Hollows FC, Coroneo MT. High dose intravitreal ganciclovir in the treatment of cytomegalovirus retinitis. Med J Aust 1992;157:370-3. Reply EDITOR: We thank Drs. Morlet, Young, and Corneo for their interest in our work on the risk fac tors for the development of retinal detachment in patients with cytomegalovirus retinitis. In deed, it was our intent in performing this study to determine risk factors not only to un derstand the pathophysiologic aspects of these retinal detachments better, but also to help devise strategies to prevent them or limit visu al morbidity because of these retinal detach ments. The risk factors that we identified in clude peripheral retinitis involving greater than 25% of the retina external to the major vascular arcades, activity of retinitis at the most recent examination. Indeed, the amount of peripheral retinitis and the presence of ac tivity of retinitis were so strong that we calcu lated that the presence of retinitis activity in over 25% of the retina external to the major vascular arcades confers a 24-fold increased risk over patients with retinitis but without these risk factors. It is logical to conclude from our study, therefore, that any measures which decrease the amount of retinal involvement with cyto megalovirus retinitis would reduce the risk of retinal detachment greatly. The currently avail able therapies for cytomegalovirus retinitis are
686
November, 1994
AMERICAN JOURNAL OF OPHTHALMOLOGY
intravenous ganciclovir or foscarnet, or both. 1 Both are associated with gradual progression of retinitis. This may be caused in part by the relatively low levels of drug that reach the in terior of the eye and the emergence of resist ance.2,3 Any intervention that will reduce the risk factors should reduce the risk of retinal detachment. It is for this reason that the data relayed by Morlet, Young, and Corneo are so interesting. The early detection of cytomegalovirus retinitis and aggressive treatment of that disease, which is being carried out at the Uni versity of New South Wales in Australia, would be expected to result in fewer cases of extensive or active cytomegalovirus retinitis, or both, and therefore lower the incidence of retinal detachment. The measures that have been instituted by this group are of interest. Others have shown that the risk of cytomega lovirus retinitis increases dramatically when the CD4 count drops below 50 per cubic milli meter (.05 x 109/1). If we assume that subclinical cytomegalovirus retinitis begins at approxi mately this CD4 count, then early detection should allow detection and treatment of le sions when they are small. Aggressive therapy would then limit reactivation and progression of disease, which should reduce the risks for rhegmatogenous retinal detachment. The use of intraocular therapy with antiviral drugs may enhance our control of retinitis. Using intrave nous therapy, reactivations occur commonly and are seen in the majority of patients within two months. Using aggressive local therapy has the potential of controlling retinitis in more cases. The issue of local versus systemic therapy is a complex one. However, there is no doubt that the use of certain types of local therapy can improve our ability to control reti nitis activity and slow or prevent the spread of retinitis into uninvolved areas of the retina. Whether this is through the use of more fre quent administration of currently available antivirals, higher doses (if safe) of new drugs, or the use of implants or other sustained-re lease vehicles placed into the vitreous is being studied. The 25% threshold at which peripheral reti nitis is associated with retinal detachment in our study was used by Morlet, Young, and Corneo as a trigger to perform scatter laser to entrap regions of retinitis. It is of great interest that in the one third of the eyes so treated
which went on to detach, the detachment was successfully entrapped by the encircling three to four rows of laser. It would be interesting to know how long the entrapped retinal detach ment remained. Additionally, it would be of interest to know if the retinal burns surround ed all lesions and were applied to the ora serrata or just to the area of the vitreous base. An important problem in designing any clinical trial to evaluate this treatment is the require ment to modify the laser treatment continu ously if the retinitis advances. We are pleased that Morlet, Young, and Cor neo have been stimulated by our work, and applaud their attempts to decrease the inci dence of retinal detachment in patients with cytomegalovirus retinitis. WILLIAM R. FREEMAN, M.D. San Diego, California DOROTHY N. FRIEDBERG, M.D. New York, New York CHARLES BERRY, PH.D. JOSE I. QUICENO, M.D. San Diego, California MARGUERITE BEHETTE, M.D. New York, New York STEVEN C. FULLERTON, M.P.H. DAVID MUNGUIA San Diego, California
References 1. Studies of Ocular Complications of AIDS (SOCA) Research Group in Collaboration with the AIDS Clinical Trials Group (ACTG). Studies of ocular complications of AIDS foscarnet-ganciclovir cyto megalovirus retinitis trial, I: rationale, designs and methods. Controlled Clin Trials 1992;13:22-39. 2. Flores-Aguilar M, Kuppermann BD, Quiceno JI, Dankner WM, Wolf DG, Caparelli EV, et al. Pathophysiology and treatment of clinically resistant cy tomegalovirus retinitis. Ophthalmology 1993;100: 1022-31. 3. Kuppermann BD, Quiceno JI, Flores-Aguilar M, Connor JD, Capparelli EV, Sherwood CH, et al. Intravitreal ganciclovir concentration after intrave nous administration in AIDS patients with cytomeg alovirus retinitis: implications for therapy. J Infect Dis 1993,168:1506-9.
ment of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis," by W. R. Freeman, D. N. Friedberg, C. Berry, j . I. Quiceno, M. Behette, S. C. Fullerton, and D. Munguia (Am. J. Ophthalmol. 116:713, De cember 1993), the authors observed that reti nal detachment complicating cytomegalovirus retinitis occurred more frequently when 25% or more of the peripheral retina was involved and when the retinitis was poorly controlled. Our current treatment of cytomegalovirus reti nitis has resulted in few retinal detachments and little loss of vision. We have achieved this by early detection through screening, 1 effective control of the retinitis, 2 and treating those most at risk of retinal detachment with prophylatic laser. We currently screen all AIDS outpatients who have a CD4 count of 0.05 x 109/1 or less every three months. We also screen AIDS pa tients admitted to the hospital for any AIDSrelated illness. Over the last two years we have screened over 270 patients and found 15 (23 eyes) with cytomegalovirus retinitis; five of those patients were asymptomatic at diagnosis. In all, 39 patients were treated for more than six weeks, 22 (35 eyes) with high-dose intravit real ganciclovir and four (seven eyes) with in travenous ganciclovir. The posterior pole was affected in nine eyes, peripheral retina in 23, and both regions in seven. Using high-dose intravitreal ganciclovir (2 mg/0.1 ml), we were able to achieve 100% resolution of the retinitis, with relapse occur ring at a median of 42 weeks in only two pa tients on weekly maintainance intravitreal in jections. The reactivation of the retinitis settled with therapy of two injections a week for three weeks. Of the four patients treated with intravenous ganciclovir, relapse occurred in three within eight weeks. For those patients who had more than 25% of the peripheral retina involved, we adminis tered laser photocoagulation as a band entrap ping the region involved. Using an argon laser and panfundoscope or three-mirror lens, we placed burns three or four deep, one spot apart, to give a full-thickness burn. Nine eyes received prophylactic laser, three of which went on to retinal detachment that was con tained by the band of laser, and visual acuity was not affected. Two patients had retinal detachments requir ing surgery. One had a small area of retinitis and responded well to a scierai buckle proce dure and intravitreal therapy. The other had extensive bilateral disease with subretinal fluid
Correspondence
685
detaching both maculae. He did poorly despite vitrectomy, silicone oil replacement, and intra venous foscarnet, never achieving good control of the retinitis or vision better than counting fingers. We look forward to a clinical trial confirming our clinical impression that early effective treatment, and prophylatic laser therapy will reduce the 25% incidence of retinal detach ment in cytomegalovirus retinitis. NIGEL MORLET, M.B., F.R.A.C.O. STEPHANIE YOUNG, M.B., F.R.A.C.O. MINAS T. CORNEO, M.S., F.R.A.C.O. Randwick, New South Wales, Australia
References 1. Morlet N, Young SR, Dean R, Gold J. Ophthalmological screening for CMV retinitis in HIV infection. Lancet 1992;340:179. 2. Young SR, Morlet N, Heery S, Hollows FC, Coroneo MT. High dose intravitreal ganciclovir in the treatment of cytomegalovirus retinitis. Med J Aust 1992;157:370-3. Reply EDITOR: We thank Drs. Morlet, Young, and Corneo for their interest in our work on the risk fac tors for the development of retinal detachment in patients with cytomegalovirus retinitis. In deed, it was our intent in performing this study to determine risk factors not only to un derstand the pathophysiologic aspects of these retinal detachments better, but also to help devise strategies to prevent them or limit visu al morbidity because of these retinal detach ments. The risk factors that we identified in clude peripheral retinitis involving greater than 25% of the retina external to the major vascular arcades, activity of retinitis at the most recent examination. Indeed, the amount of peripheral retinitis and the presence of ac tivity of retinitis were so strong that we calcu lated that the presence of retinitis activity in over 25% of the retina external to the major vascular arcades confers a 24-fold increased risk over patients with retinitis but without these risk factors. It is logical to conclude from our study, therefore, that any measures which decrease the amount of retinal involvement with cyto megalovirus retinitis would reduce the risk of retinal detachment greatly. The currently avail able therapies for cytomegalovirus retinitis are
686
November, 1994
AMERICAN JOURNAL OF OPHTHALMOLOGY
intravenous ganciclovir or foscarnet, or both. 1 Both are associated with gradual progression of retinitis. This may be caused in part by the relatively low levels of drug that reach the in terior of the eye and the emergence of resist ance.2,3 Any intervention that will reduce the risk factors should reduce the risk of retinal detachment. It is for this reason that the data relayed by Morlet, Young, and Corneo are so interesting. The early detection of cytomegalovirus retinitis and aggressive treatment of that disease, which is being carried out at the Uni versity of New South Wales in Australia, would be expected to result in fewer cases of extensive or active cytomegalovirus retinitis, or both, and therefore lower the incidence of retinal detachment. The measures that have been instituted by this group are of interest. Others have shown that the risk of cytomega lovirus retinitis increases dramatically when the CD4 count drops below 50 per cubic milli meter (.05 x 109/1). If we assume that subclinical cytomegalovirus retinitis begins at approxi mately this CD4 count, then early detection should allow detection and treatment of le sions when they are small. Aggressive therapy would then limit reactivation and progression of disease, which should reduce the risks for rhegmatogenous retinal detachment. The use of intraocular therapy with antiviral drugs may enhance our control of retinitis. Using intrave nous therapy, reactivations occur commonly and are seen in the majority of patients within two months. Using aggressive local therapy has the potential of controlling retinitis in more cases. The issue of local versus systemic therapy is a complex one. However, there is no doubt that the use of certain types of local therapy can improve our ability to control reti nitis activity and slow or prevent the spread of retinitis into uninvolved areas of the retina. Whether this is through the use of more fre quent administration of currently available antivirals, higher doses (if safe) of new drugs, or the use of implants or other sustained-re lease vehicles placed into the vitreous is being studied. The 25% threshold at which peripheral reti nitis is associated with retinal detachment in our study was used by Morlet, Young, and Corneo as a trigger to perform scatter laser to entrap regions of retinitis. It is of great interest that in the one third of the eyes so treated
which went on to detach, the detachment was successfully entrapped by the encircling three to four rows of laser. It would be interesting to know how long the entrapped retinal detach ment remained. Additionally, it would be of interest to know if the retinal burns surround ed all lesions and were applied to the ora serrata or just to the area of the vitreous base. An important problem in designing any clinical trial to evaluate this treatment is the require ment to modify the laser treatment continu ously if the retinitis advances. We are pleased that Morlet, Young, and Cor neo have been stimulated by our work, and applaud their attempts to decrease the inci dence of retinal detachment in patients with cytomegalovirus retinitis. WILLIAM R. FREEMAN, M.D. San Diego, California DOROTHY N. FRIEDBERG, M.D. New York, New York CHARLES BERRY, PH.D. JOSE I. QUICENO, M.D. San Diego, California MARGUERITE BEHETTE, M.D. New York, New York STEVEN C. FULLERTON, M.P.H. DAVID MUNGUIA San Diego, California
References 1. Studies of Ocular Complications of AIDS (SOCA) Research Group in Collaboration with the AIDS Clinical Trials Group (ACTG). Studies of ocular complications of AIDS foscarnet-ganciclovir cyto megalovirus retinitis trial, I: rationale, designs and methods. Controlled Clin Trials 1992;13:22-39. 2. Flores-Aguilar M, Kuppermann BD, Quiceno JI, Dankner WM, Wolf DG, Caparelli EV, et al. Pathophysiology and treatment of clinically resistant cy tomegalovirus retinitis. Ophthalmology 1993;100: 1022-31. 3. Kuppermann BD, Quiceno JI, Flores-Aguilar M, Connor JD, Capparelli EV, Sherwood CH, et al. Intravitreal ganciclovir concentration after intrave nous administration in AIDS patients with cytomeg alovirus retinitis: implications for therapy. J Infect Dis 1993,168:1506-9.