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Herpetic Keratitis and Keratoconjunctivitis
SUMMARY OF THE SYMPOSIUM
165
veloped typical epidemic keratoconjunctivitis; studied by virus isolation and antibody titer the fifth had specific antibodies to adenovirus determinations. 2. Additional volunteers should be inocu type 8 at the time of inoculation and remained well. The uninoculated eye became involved lated with the recovered agents, their clinical in three volunteers six to eight days after the and serologic responses should be noted, and inoculated eye. Adenovirus type 8 was re- the viral agent re-isolated. 3. In serologic surveys, the incidence of isolated from the lesions and the volunteers developed significant antibody titer rises. specific antibodies to isolated agents should Work is currently in progress to establish be compared in typical and atypical cases whether vaccination of volunteers with adeno diagnosed as epidemic keratoconjunctivitis, in virus type 8 will prevent the development of other eye diseases, and in comparable control epidemic keratoconjunctivitis upon subse populations. quent inoculation of the eye with the agent. 4. The agents isolated in various parts of The position of the so-called "Sanders the world should be exchanged by different virus" of epidemic keratoconjunctivitis was laboratories in efforts to obtain confirmation discussed at length. This agent was originally of results. implicated in the epidemic keratoconjuncti HERPETIC KERATITIS AND vitis epidemics of 1940-42. At that time it KERATOCONJUNCTIVITIS was isolated repeatedly by Dr. Murray Sand There was general agreement that the ers from typical cases and gave serologic re actions with these patients' sera. The subse problems of herpetic keratitis and conjunc quent fate of this virus is not known, but in tivitis have become more important since 1947 the agent carrying the label of "EKC the war and since the introduction of corti virus"—perhaps derived from the original sone and related steroids for topical use in isolation—was a variant of St. Louis en ocular infections. cephalitis virus and had no serologic relation There seemed to be general agreement that ship to the epidemic keratoconjunctivitis primary herpetic infection of the eye may cases which occurred between 1947 and 1955. occur in children as a severe keratoconjunc While there was much speculation concerning tivitis but that, in the secondary forms, the this confusing situation, no final solution to conjunctiva is usually spared and the cornea the riddle was forthcoming. It was felt that alone involved. It was also agreed that her an exact repetition of the efforts of Dr. petic keratitis appears typically as a dendritic Sanders in 1940 was not indicated because of keratitis but that a variety of other super the high probability that in repeated animal ficial and deep forms can occur, and that of passage a latent virus would be "picked up" these the most important is the so-called "hyaccidentally. This has already occurred in the popyon keratitis" whose exact nature needs hands of some workers. Thus it was con elucidation. The consensus was that the ma cluded that (a) the nature and fate of the jority of cases of hypopyon develop as a re original "Sanders virus" remains uncertain, sult of secondary bacterial or mycotic in and (b) the strains of that virus currently fection, but the University of California available bear no evident relationship to the group felt that, at least in certain cases, the disease epidemic keratoconjunctivitis as it action of herpes simplex virus alone is re exists at the present time. sponsible. Further investigation of the nonThe following points should be pursued dendritic forms of herpetic keratitis is much in order to establish the etiology of epidemic needed. keratoconjunctivitis on firm ground: There was discussion of the possibility that 1. In epidemics occurring in various parts some cases of dendritic keratitis in adults of the world, entirely typical cases should be may represent primary infection. In view of
166
SUMMARY OF THE SYMPOSIUM
the paucity of available evidence, however, no conclusion could be reached. The problem needs further serologic work. The role of steroid therapy in the develop ment of chronicity and other complications in herpetic keratitis was then discussed. There seemed to be general agreement that the widespread topical use of the steroid hor mones has contributed to the relatively high frequency of complications noted in the post war years. Further experimental work is needed to determine whether this effect is due to increased proliferation of virus in the tis sues or to an unfavorable effect on the tissues themselves. Among the many questions that were raised and left unanswered concerning im munity in herpetic keratitis and conjuncti vitis, two of the more important were: 1. Does the presence of antibodies pro tect the conjunctiva from involvement in corneal relapses? 2. When a conjunctivitis occurs in a re lapse, as occasionally happens, does this al ways indicate the presence of secondary in fection with bacteria or other agents? It was agreed that herpes-simplex virus could be isolated with great ease from typi cal epithelial corneal lesions early in the dis ease, but only with great difficulty and infre quently from stromal lesions, and that it is isolated very infrequently in the absence of
clinical herpetic disease. Its possible presence in the "latent stage" in the eye could thus lead to confusing laboratory results. The mean ing of "latency" in herpes simplex and the problems concerned with the unmasking of latent viruses were discussed in detail. Many questions dealing with primary in fection versus recurrence were also ex amined. Does a recurrence always indicate that the same tissue area was involved in the primary infection ? May a dendritic keratitis occurring for the (apparently) first time late in life be a primary infection, or is it always a recurrence of an infection 20 or 30 years before? In "latency" is the virus in an incomplete ("provirus") form requiring activation by the trigger mechanism to be come infective, or is there infective virus present within certain cell groups which spreads when the close symbiotic relationship is disturbed by the trigger? Is the infection with herpes virus so strictly limited to the corneal epithelium that its total removal by curettage, or in the course of corneal graft ing, may lead to permanent security from re lapse ? The lack of unanimity of opinion on these questions suggested an urgent need for fur ther investigative work. Phillips Thygeson. Ernest Jawetz.
165
veloped typical epidemic keratoconjunctivitis; studied by virus isolation and antibody titer the fifth had specific antibodies to adenovirus determinations. 2. Additional volunteers should be inocu type 8 at the time of inoculation and remained well. The uninoculated eye became involved lated with the recovered agents, their clinical in three volunteers six to eight days after the and serologic responses should be noted, and inoculated eye. Adenovirus type 8 was re- the viral agent re-isolated. 3. In serologic surveys, the incidence of isolated from the lesions and the volunteers developed significant antibody titer rises. specific antibodies to isolated agents should Work is currently in progress to establish be compared in typical and atypical cases whether vaccination of volunteers with adeno diagnosed as epidemic keratoconjunctivitis, in virus type 8 will prevent the development of other eye diseases, and in comparable control epidemic keratoconjunctivitis upon subse populations. quent inoculation of the eye with the agent. 4. The agents isolated in various parts of The position of the so-called "Sanders the world should be exchanged by different virus" of epidemic keratoconjunctivitis was laboratories in efforts to obtain confirmation discussed at length. This agent was originally of results. implicated in the epidemic keratoconjuncti HERPETIC KERATITIS AND vitis epidemics of 1940-42. At that time it KERATOCONJUNCTIVITIS was isolated repeatedly by Dr. Murray Sand There was general agreement that the ers from typical cases and gave serologic re actions with these patients' sera. The subse problems of herpetic keratitis and conjunc quent fate of this virus is not known, but in tivitis have become more important since 1947 the agent carrying the label of "EKC the war and since the introduction of corti virus"—perhaps derived from the original sone and related steroids for topical use in isolation—was a variant of St. Louis en ocular infections. cephalitis virus and had no serologic relation There seemed to be general agreement that ship to the epidemic keratoconjunctivitis primary herpetic infection of the eye may cases which occurred between 1947 and 1955. occur in children as a severe keratoconjunc While there was much speculation concerning tivitis but that, in the secondary forms, the this confusing situation, no final solution to conjunctiva is usually spared and the cornea the riddle was forthcoming. It was felt that alone involved. It was also agreed that her an exact repetition of the efforts of Dr. petic keratitis appears typically as a dendritic Sanders in 1940 was not indicated because of keratitis but that a variety of other super the high probability that in repeated animal ficial and deep forms can occur, and that of passage a latent virus would be "picked up" these the most important is the so-called "hyaccidentally. This has already occurred in the popyon keratitis" whose exact nature needs hands of some workers. Thus it was con elucidation. The consensus was that the ma cluded that (a) the nature and fate of the jority of cases of hypopyon develop as a re original "Sanders virus" remains uncertain, sult of secondary bacterial or mycotic in and (b) the strains of that virus currently fection, but the University of California available bear no evident relationship to the group felt that, at least in certain cases, the disease epidemic keratoconjunctivitis as it action of herpes simplex virus alone is re exists at the present time. sponsible. Further investigation of the nonThe following points should be pursued dendritic forms of herpetic keratitis is much in order to establish the etiology of epidemic needed. keratoconjunctivitis on firm ground: There was discussion of the possibility that 1. In epidemics occurring in various parts some cases of dendritic keratitis in adults of the world, entirely typical cases should be may represent primary infection. In view of
166
SUMMARY OF THE SYMPOSIUM
the paucity of available evidence, however, no conclusion could be reached. The problem needs further serologic work. The role of steroid therapy in the develop ment of chronicity and other complications in herpetic keratitis was then discussed. There seemed to be general agreement that the widespread topical use of the steroid hor mones has contributed to the relatively high frequency of complications noted in the post war years. Further experimental work is needed to determine whether this effect is due to increased proliferation of virus in the tis sues or to an unfavorable effect on the tissues themselves. Among the many questions that were raised and left unanswered concerning im munity in herpetic keratitis and conjuncti vitis, two of the more important were: 1. Does the presence of antibodies pro tect the conjunctiva from involvement in corneal relapses? 2. When a conjunctivitis occurs in a re lapse, as occasionally happens, does this al ways indicate the presence of secondary in fection with bacteria or other agents? It was agreed that herpes-simplex virus could be isolated with great ease from typi cal epithelial corneal lesions early in the dis ease, but only with great difficulty and infre quently from stromal lesions, and that it is isolated very infrequently in the absence of
clinical herpetic disease. Its possible presence in the "latent stage" in the eye could thus lead to confusing laboratory results. The mean ing of "latency" in herpes simplex and the problems concerned with the unmasking of latent viruses were discussed in detail. Many questions dealing with primary in fection versus recurrence were also ex amined. Does a recurrence always indicate that the same tissue area was involved in the primary infection ? May a dendritic keratitis occurring for the (apparently) first time late in life be a primary infection, or is it always a recurrence of an infection 20 or 30 years before? In "latency" is the virus in an incomplete ("provirus") form requiring activation by the trigger mechanism to be come infective, or is there infective virus present within certain cell groups which spreads when the close symbiotic relationship is disturbed by the trigger? Is the infection with herpes virus so strictly limited to the corneal epithelium that its total removal by curettage, or in the course of corneal graft ing, may lead to permanent security from re lapse ? The lack of unanimity of opinion on these questions suggested an urgent need for fur ther investigative work. Phillips Thygeson. Ernest Jawetz.