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Corneal Changes in Tric Agent Infections
CORNEAL CHANGES IN TRIC AGENT I N F E C T I O N S PHILLIPS T I
Until recently it was generally believed that trachoma and inclusion conjunctivitis could be differentiated without difficulty on the basis of clinical course, trachoma leading eventually to conjunctival scars, pannus and corneal scars, and inclusion conjunctivitis healing spontaneously without scars or pan nus. The benign character of the clinical course of inclusion conjunctivitis of the newborn has not been questioned, but re cently, particularly as a result of the work of Jones 1 in London, the difficulty of differentiating the two diseases in adults, particularly at onset, has been given special attention. Underscoring the problem, Jones and Collier2 produced a severe, trachomalike disease with scars and pannus by the exper imental inoculation of a human volunteer with a TRIC agent isolated from inclusion conjunctivitis of the newborn. As described elsewhere in this symposi um, San Francisco cases believed to be adult forms of inclusion conjunctivitis have also developed types of keratitis (including micropannus and subepithelial infiltrates) not previously identified with inclusion conjunc tivitis. Further confusing the picture, human volunteers inoculated experimentally with two strains isolated from the disease in the newborn have developed round, subepi thelial infiltrates of the type previously con sidered pathognomonic of epidemic keratoconjunctivitis (EKC) ; these have also been seen, though much less frequently, in natu rally occurring adult inclusion conjunctivi tis. Simultaneously, atypical trachoma with a benign course, free from pannus and From the Francis I. Proctor Foundation for Research in Ophthalmology and the Department of Ophthalmology, University of California San Francisco Medical Center. Reprint requests to: Dr. Phillips Thygeson, Francis I. Proctor Foundation, San Francisco Medical Center, School of Medicine, San Fran cisco, California 94122.
GESON, M . D .
keratitis but yielding TRIC isolates, is being reported from South Africa.3 These and other clinical observations, combined with the fact that trachoma and inclusion conjunctivitis isolates cannot be differentiated in the laboratory, have per suaded some investigators to regard the two conditions as manifestations of the same disease. It has even been suggested that lymphogranuloma venereum (LGV) is part of the same complex. This suggestion of course ignores the fact that LGV, with its startling affinity for the lymph vessels, pro duces lymph blockage and buboes not found in trachoma or inclusion conjunctivitis and has very little in common with the TRIC agent diseases. In the hope of shedding a little light on this puzzling question, the corneal changes in trachoma have been scrutinized and their characteristics and diagnostic value reas sessed. CLINICAL DIAGNOSIS OF TRACHOMA
The diagnosis of trachoma is perforce a clinical one, based on both conjunctival and corneal signs. A presumptive or a definitive clinical diagnosis can be made on the pres ence or absence of the cardinal signs of the disease. These are (1) follicular hypertro phy with prominent involvement of the upper tarsal follicles; (2) conjunctival cica trization, predominantly of the upper tarsal conjunctiva and fornix; (3) microscopic or gross pannus, predominantly of the upper quadrants; and (4) limbal follicles or their cicatricial remains, Herbert's peripheral pits. For the purposes of this study, the cri teria for a presumptive diagnosis were signs (1) and (3), and for a definitive diagnosis a combination of signs (1), (2) and (3). If sign (4) was present, however, a definitive diagnosis could be made in the absence of cicatrization or gross pannus.
TRACHOMA AND ALLIED DISEASES
1279/253
The study here reported is based on ob servations made on trachoma in the white, Indian, and Mexican populations of Cali fornia and the southwestern States. As re ported in a previous communication,4 tra choma in school children, particularly In dian school children, differs considerably from trachoma in adults. The more promi nent corneal changes of the adult disease markedly increase the severity of the symp toms. When trachoma has been contracted in adult life, an acute onset, florid evolution, and severe corneal changes have been the rule. In addition to the naturally occurring cases that have been observed, a single case of experimental trachoma produced in a blind volunteer has provided interesting in formation on the corneal changes of the early stages of the disease; it was possible to follow their evolution in this volunteer over a four-month period.
children, many children with inclusion con junctivitis were examined in the past in con nection with various swimming pool epi demics. No subepithelial corneal changes or micropannus were seen in any of these chil dren, and Allen5 failed to find any corneal changes whatever in the cases of experimen tal inclusion conjunctivitis in school children studied by him. In Indian high school children, conjunctival scars and gross pannus have often been seen, along with a high incidence of Her bert's pits. More florid cases of follicular trachoma have been seen in this age group, and epithelial keratitis and subepithelial infiltrates have been more prominent than in the younger age group. Nevertheless, no example of the EKC type of round, subepi thelial infiltrate has ever been observed in these children, the great majority of whom were initially infected at a preschool age.
CORNEAL CHANGES I N
CORNEAL CHANGES IN
CHILDHOOD TRACHOMA
ADULT TRACHOMA
Trachoma of grade school children as seen in Indian schools in Arizona and New Mexico was characterized by insidious onset, minimal symptoms and chronic course. Corneal changes were limited in these cases to (1) minute fluorescein-staining epithelial lesions most prominent su periorly; (2) small, flecklike subepithelial infiltrates limited to the upper quadrants; (3) micropannus varying from 0.5 mm to 2.0 mm ; and (4) (occasionally) limbal folli cles or Herbert's pits. No example of the EKC type of grossly visible, round, coinlike subepithelial infiltrates was seen in any of the many hundreds of grade school children observed by me in the course of routine di agnostic school examinations, or in any grade school child in the course of my ex aminations as consultant to the Division of Indian Health, or in any white or Mexican grade school child examined in surveys made for the California State Health De partment. Although I have not recently seen any inclusion conjunctivitis in grade school
Trachoma patients seen in the San Fran cisco Bay area who contracted their tracho ma in adult life have always had a history of acute or subacute onset, never of an in sidious onset. Unlike trachomatous children, they never have been in doubt as to the day of the onset of their symptoms. It has been difficult to make even a presumptive diag nosis of these cases early in their develop ment because of their similarity to cases of adult inclusion conjunctivitis. Diagnosis has often required observation over a period of weeks or months without treatment. Re ferred untreated cases of several months' or more duration have been easier to diagnose on the basis of the limbal and corneal changes that have almost invariably been in evidence. EKC-like opacities, although extremely rare, did occur in small numbers in two cases. Unlike the opacities of EKC, how ever, they did not disappear with time. For this reason it seems probable that they were in fact trachoma pustules resulting from
1280/254
AMERICAN JOURNAL OF OPHTHALMOLOGY
leukocytic infiltration rather than the nonnecrotizing type of infiltrate seen in adenovirus type 8 infection. In working with tra choma in our Indian population since 1928, first as a consultant to the Bureau of Indian Affairs and since 1950 as a consultant to the Division of Indian Health, I have surveyed several entire Indian populations, as for ex ample, the White Mountain Apaches. In none of these surveys have I encountered a trachomatous keratitis that could be confused with EKC or with the type of keratitis with round infiltrates that has recently been seen by us in volunteers inoculated with two in clusion conjunctivitis agents. The corneal picture in adult trachoma was well illustrated by the disease induced ex perimentally in the left eye of a blind volun teer (A. B., aged 48 years) with Apache 2 trachoma strain. The progression of signs in this eye, observed over a four-month pe riod, is representative of the disease picture of adult trachoma as it has been seen in the San Francisco Bay area. Simultaneously with the development of conjunctival inflammation and exudate, a fluorescein-staining epithelial keratitis ap peared that involved the entire cornea but was much more prominent superiorly. There then developed a swelling of the limbus, again most marked superiorly, which was soon followed by the appearance of small, irregularly-shaped, grayish, subepithelial infiltrates involving the upper quad rants. About 10 days after the onset of the experimental disease, extension of limbal vessels was noted, and within the next 10 days a micropannus that measured 1.0 mm in length at the 12-o'clock position had be come well established. By then there was also considerable cellular infiltration at the limbus, replacing the previous edema. As the disease progressed, there was gradual but uniform extension of vessels so that at the end of four months the pannus was grossly visible and could be photo graphed well. During the later months of the disease, the subepithelial infiltrates be
MAY, 1967
came more prominent, both within the meshwork of the pannus vessels and in ad vance of the vessels. Near the limbus a few large infiltrates developed, and opposite them, at the 10- and 2-o'clock positions, there was increased vascularity. No typical trachoma pustules or ulcération developed, and no limbal follicles were seen. The corneal picture just described is typi cal of that of the majority of trachoma cases seen in adults in this study. In a few cases that had persisted for months, there were also limbal follicles and trachoma pustules that underwent ulcération. Figures 1-3 illustrate the characteristic changes of adult trachoma. DISCUSSION
It is unfortunate that the diagnosis of tra choma must still depend on clinical findings, but fortunate that trachoma in its estab lished, cicatricial stage (Stage III, MacCallan) is one of the best defined clinical enti ties known to medicine. There are few dis eases that have such characteristic clinical signs. Only in the early, precicatricial stages is diagnosis a problem. The diagnostic value of the early corneal changes in trachoma has rightly received much attention, particularly in connection with the differentiation of tra choma from the various types of follicular conjunctivitis. The complete corneal picture, which includes micropannus located su-
Fig. 1 (Thygeson). Corneal changes in adult Caucasian trachoma, Stage Ha (MacCallan), show-' ing early pannus, one large round infiltrate (tra choma pustule), and many small subepithelial in filtrates.
TRACHOMA AND ALLIED DISEASES
Fig. 2 (Thygeson). Early changes in adult Cau casian trachoma of several months' duration (Stage lib), showing pannus, subepithelial infiltrates be yond the pannus, and one large subepithelial in filtrate which later ulcerated.
1281/255
their diagnostic significance. It is essential, moreover, that the EKC type of benign sub epithelial opacity should be distinguished from the trachoma "pustule" which, like the nummular opacity of nummular keratitis, tends to leave a permanent round cicatrix. None of our naturally occurring San Fran cisco cases of inclusion conjunctivitis of any age have had opacities comparable to the trachoma pustule or the necrotizing round opacity of nummular keratitis, or have de veloped gross pannus. It is still too early to tell whether any of our experimental inocu lations with inclusion conjunctivitis agents have produced permanent opacities, but no case has as yet shown gross pannus or diffuse corneal scarring. In TRIC agent studies, particularly when attempts are being made to differentiate iso lates from trachoma and inclusion conjunc tivitis, it is essential that a definitive diag nosis of the disease from which the isolate was recovered be made whenever possible. If it is possible to make only a presumptive di agnosis of either trachoma or inclusion con junctivitis, this should be so stated in the report. SUMMARY AND CONCLUSIONS
Fig. 3 (Thygeson). Trachoma of six months' duration in a Caucasian adult, showing gross pan nus extending into the pupil and two well-devel oped limbal follicles. periorly, epithelial keratitis, subepithelial infiltrates, and limbal follicles, is unequiv ocally diagnostic, but without the limbal fol licles or Herbert's pits its diagnostic value is reduced markedly. It can now be stated cat egorically that upper-quadrant micropannus alone has lost much of its diagnostic value since it is also found occasionally in nontrachomatous disease. In view of the importance ascribed by the London observers to the so-called "punctate lesions" of trachoma and inclusion conjunc tivitis, some consideration must be given to
1. The corneal changes of trachoma in Indian, Mexican and white school children have been mild but useful in making pre sumptive and definitive clinical diagnoses of trachoma. 2. In adult trachoma in which gross pan nus and conjunctival cicatrization have de veloped, no difficulty has been encountered in the differential diagnosis from adult inclusion conjunctivitis. In the early stages, however, differential diagnosis may be difficult, and repeated examination of the untreated case may be necessary. 3. The trachomatous keratitis seen in pa tients in the San Francisco area and the southwestern United States differs in no major respect from trachomatous keratitis seen in other parts of the world. 4. Gross pannus, limbal follicles, or Her-
1282/256
AMERICAN JOURNAL OF OPHTHALMOLOGY
bert's peripheral pits never have been seen in inclusion conjunctivitis in the San Fran cisco area. This applies equally to the natu rally occurring and the experimentally pro duced disease. 5. The importance of micropannus as a diagnostic sign of trachoma is lessened by its occasional occurrence in vernal catarrh, adult inclusion conjunctivitis, superior limbic keratoconjunctivitis, allergic marginal infiltration, etc.
MAY, 1967
REFERENCES
1. Jones, B. R.: Ocular syndromes of TRIC virus infection and their possible genital signifi cance. Brit J. Ven. Dis. 40:3, 1964. 2. Jones, B. R. and Collier, L. H. : Inoculation of man with inclusion blennorrhea virus. Ann. N. Y.Acad. Sci. 98:212,1962. 3. Scott, J. G. (Johannesburg, South Africa). Personal communication. 4. Thygeson, P. and Dawson, C. R.: Trachoma and follicular conjunctivitis in children. Arch. Ophth. 75:3, 1966. 5. Allen, J. H. : Inclusion blennorrhea. Am. J. Ophth. 27 :833, 1944.
STUDIES ON OCULOGENITAL T R I C AGENTS ISOLATED IN DENMARK C. H.
MORDHORST,
During the last 30 to 40 years it has been commonly agreed that trachoma is not a problem in Denmark. The diagnosis of in clusion conjunctivitis and inclusion blennorrhea has never been fully established here. Since the reports of T'ang and coworkers 1 of successful attempts to grow tra choma agents in the yolk sac of embryonated eggs, improved diagnostic techniques have been available. By means of these tech niques, special clinical and laboratory efforts have been made during the past four years to detect the presence of TRIC agent infec tions among Danish eye patients. Over this four-year period, more than 200 eye patients have been examined for a possible TRIC agent infection. Most of them were referred because of symptoms of a chronic or recurrent conjunctivitis or ker atoconjunctivitis of unknown etiology. In about 35 subjects, a clinical diagnosis of tra choma or inclusion conjunctivitis could not be ruled out at the first examination; how ever, repeated search for the presence of From the Ornithosis Department, Statens Seruminstitut, Copenhagen, Denmark. Reprint requests to: Dr. C. H. Mordhorst, Statens Seruminstitut, Amager Boulevard 80, Co penhagen, Denmark.
M.D.
conjunctival inclusion bodies, and attempts to isolate TRIC agents in eggs, were all un successful. Left were 19 individuals with a presumptive clinical diagnosis of a TRIC agent disease. Laboratory studies on con junctival scrapings from all of these pa tients, in conjunction with similar studies of genital scrapings from some of the cases, have now been completed. In addition, geni tal examinations for a TRIC agent infection among 18 individuals who were associated with the eye patients infected with TRIC agent have been carried out. The preliminary results of these investi gations were reported previously.2"4 The present paper summarizes the final results of this study of the oculogenital TRIC agent infections observed during the survey mentioned above. MATERIALS AND METHODS
Detailed descriptions of techniques em ployed have been published elsewhere,3 and only data pertinent to this presentation will be given here. Patients. A majority of patients were ex amined at the Out-Patient Clinic of the De partment of Ophthalmology, Rigshospitalet, University of Copenhagen. All the newborn
Until recently it was generally believed that trachoma and inclusion conjunctivitis could be differentiated without difficulty on the basis of clinical course, trachoma leading eventually to conjunctival scars, pannus and corneal scars, and inclusion conjunctivitis healing spontaneously without scars or pan nus. The benign character of the clinical course of inclusion conjunctivitis of the newborn has not been questioned, but re cently, particularly as a result of the work of Jones 1 in London, the difficulty of differentiating the two diseases in adults, particularly at onset, has been given special attention. Underscoring the problem, Jones and Collier2 produced a severe, trachomalike disease with scars and pannus by the exper imental inoculation of a human volunteer with a TRIC agent isolated from inclusion conjunctivitis of the newborn. As described elsewhere in this symposi um, San Francisco cases believed to be adult forms of inclusion conjunctivitis have also developed types of keratitis (including micropannus and subepithelial infiltrates) not previously identified with inclusion conjunc tivitis. Further confusing the picture, human volunteers inoculated experimentally with two strains isolated from the disease in the newborn have developed round, subepi thelial infiltrates of the type previously con sidered pathognomonic of epidemic keratoconjunctivitis (EKC) ; these have also been seen, though much less frequently, in natu rally occurring adult inclusion conjunctivi tis. Simultaneously, atypical trachoma with a benign course, free from pannus and From the Francis I. Proctor Foundation for Research in Ophthalmology and the Department of Ophthalmology, University of California San Francisco Medical Center. Reprint requests to: Dr. Phillips Thygeson, Francis I. Proctor Foundation, San Francisco Medical Center, School of Medicine, San Fran cisco, California 94122.
GESON, M . D .
keratitis but yielding TRIC isolates, is being reported from South Africa.3 These and other clinical observations, combined with the fact that trachoma and inclusion conjunctivitis isolates cannot be differentiated in the laboratory, have per suaded some investigators to regard the two conditions as manifestations of the same disease. It has even been suggested that lymphogranuloma venereum (LGV) is part of the same complex. This suggestion of course ignores the fact that LGV, with its startling affinity for the lymph vessels, pro duces lymph blockage and buboes not found in trachoma or inclusion conjunctivitis and has very little in common with the TRIC agent diseases. In the hope of shedding a little light on this puzzling question, the corneal changes in trachoma have been scrutinized and their characteristics and diagnostic value reas sessed. CLINICAL DIAGNOSIS OF TRACHOMA
The diagnosis of trachoma is perforce a clinical one, based on both conjunctival and corneal signs. A presumptive or a definitive clinical diagnosis can be made on the pres ence or absence of the cardinal signs of the disease. These are (1) follicular hypertro phy with prominent involvement of the upper tarsal follicles; (2) conjunctival cica trization, predominantly of the upper tarsal conjunctiva and fornix; (3) microscopic or gross pannus, predominantly of the upper quadrants; and (4) limbal follicles or their cicatricial remains, Herbert's peripheral pits. For the purposes of this study, the cri teria for a presumptive diagnosis were signs (1) and (3), and for a definitive diagnosis a combination of signs (1), (2) and (3). If sign (4) was present, however, a definitive diagnosis could be made in the absence of cicatrization or gross pannus.
TRACHOMA AND ALLIED DISEASES
1279/253
The study here reported is based on ob servations made on trachoma in the white, Indian, and Mexican populations of Cali fornia and the southwestern States. As re ported in a previous communication,4 tra choma in school children, particularly In dian school children, differs considerably from trachoma in adults. The more promi nent corneal changes of the adult disease markedly increase the severity of the symp toms. When trachoma has been contracted in adult life, an acute onset, florid evolution, and severe corneal changes have been the rule. In addition to the naturally occurring cases that have been observed, a single case of experimental trachoma produced in a blind volunteer has provided interesting in formation on the corneal changes of the early stages of the disease; it was possible to follow their evolution in this volunteer over a four-month period.
children, many children with inclusion con junctivitis were examined in the past in con nection with various swimming pool epi demics. No subepithelial corneal changes or micropannus were seen in any of these chil dren, and Allen5 failed to find any corneal changes whatever in the cases of experimen tal inclusion conjunctivitis in school children studied by him. In Indian high school children, conjunctival scars and gross pannus have often been seen, along with a high incidence of Her bert's pits. More florid cases of follicular trachoma have been seen in this age group, and epithelial keratitis and subepithelial infiltrates have been more prominent than in the younger age group. Nevertheless, no example of the EKC type of round, subepi thelial infiltrate has ever been observed in these children, the great majority of whom were initially infected at a preschool age.
CORNEAL CHANGES I N
CORNEAL CHANGES IN
CHILDHOOD TRACHOMA
ADULT TRACHOMA
Trachoma of grade school children as seen in Indian schools in Arizona and New Mexico was characterized by insidious onset, minimal symptoms and chronic course. Corneal changes were limited in these cases to (1) minute fluorescein-staining epithelial lesions most prominent su periorly; (2) small, flecklike subepithelial infiltrates limited to the upper quadrants; (3) micropannus varying from 0.5 mm to 2.0 mm ; and (4) (occasionally) limbal folli cles or Herbert's pits. No example of the EKC type of grossly visible, round, coinlike subepithelial infiltrates was seen in any of the many hundreds of grade school children observed by me in the course of routine di agnostic school examinations, or in any grade school child in the course of my ex aminations as consultant to the Division of Indian Health, or in any white or Mexican grade school child examined in surveys made for the California State Health De partment. Although I have not recently seen any inclusion conjunctivitis in grade school
Trachoma patients seen in the San Fran cisco Bay area who contracted their tracho ma in adult life have always had a history of acute or subacute onset, never of an in sidious onset. Unlike trachomatous children, they never have been in doubt as to the day of the onset of their symptoms. It has been difficult to make even a presumptive diag nosis of these cases early in their develop ment because of their similarity to cases of adult inclusion conjunctivitis. Diagnosis has often required observation over a period of weeks or months without treatment. Re ferred untreated cases of several months' or more duration have been easier to diagnose on the basis of the limbal and corneal changes that have almost invariably been in evidence. EKC-like opacities, although extremely rare, did occur in small numbers in two cases. Unlike the opacities of EKC, how ever, they did not disappear with time. For this reason it seems probable that they were in fact trachoma pustules resulting from
1280/254
AMERICAN JOURNAL OF OPHTHALMOLOGY
leukocytic infiltration rather than the nonnecrotizing type of infiltrate seen in adenovirus type 8 infection. In working with tra choma in our Indian population since 1928, first as a consultant to the Bureau of Indian Affairs and since 1950 as a consultant to the Division of Indian Health, I have surveyed several entire Indian populations, as for ex ample, the White Mountain Apaches. In none of these surveys have I encountered a trachomatous keratitis that could be confused with EKC or with the type of keratitis with round infiltrates that has recently been seen by us in volunteers inoculated with two in clusion conjunctivitis agents. The corneal picture in adult trachoma was well illustrated by the disease induced ex perimentally in the left eye of a blind volun teer (A. B., aged 48 years) with Apache 2 trachoma strain. The progression of signs in this eye, observed over a four-month pe riod, is representative of the disease picture of adult trachoma as it has been seen in the San Francisco Bay area. Simultaneously with the development of conjunctival inflammation and exudate, a fluorescein-staining epithelial keratitis ap peared that involved the entire cornea but was much more prominent superiorly. There then developed a swelling of the limbus, again most marked superiorly, which was soon followed by the appearance of small, irregularly-shaped, grayish, subepithelial infiltrates involving the upper quad rants. About 10 days after the onset of the experimental disease, extension of limbal vessels was noted, and within the next 10 days a micropannus that measured 1.0 mm in length at the 12-o'clock position had be come well established. By then there was also considerable cellular infiltration at the limbus, replacing the previous edema. As the disease progressed, there was gradual but uniform extension of vessels so that at the end of four months the pannus was grossly visible and could be photo graphed well. During the later months of the disease, the subepithelial infiltrates be
MAY, 1967
came more prominent, both within the meshwork of the pannus vessels and in ad vance of the vessels. Near the limbus a few large infiltrates developed, and opposite them, at the 10- and 2-o'clock positions, there was increased vascularity. No typical trachoma pustules or ulcération developed, and no limbal follicles were seen. The corneal picture just described is typi cal of that of the majority of trachoma cases seen in adults in this study. In a few cases that had persisted for months, there were also limbal follicles and trachoma pustules that underwent ulcération. Figures 1-3 illustrate the characteristic changes of adult trachoma. DISCUSSION
It is unfortunate that the diagnosis of tra choma must still depend on clinical findings, but fortunate that trachoma in its estab lished, cicatricial stage (Stage III, MacCallan) is one of the best defined clinical enti ties known to medicine. There are few dis eases that have such characteristic clinical signs. Only in the early, precicatricial stages is diagnosis a problem. The diagnostic value of the early corneal changes in trachoma has rightly received much attention, particularly in connection with the differentiation of tra choma from the various types of follicular conjunctivitis. The complete corneal picture, which includes micropannus located su-
Fig. 1 (Thygeson). Corneal changes in adult Caucasian trachoma, Stage Ha (MacCallan), show-' ing early pannus, one large round infiltrate (tra choma pustule), and many small subepithelial in filtrates.
TRACHOMA AND ALLIED DISEASES
Fig. 2 (Thygeson). Early changes in adult Cau casian trachoma of several months' duration (Stage lib), showing pannus, subepithelial infiltrates be yond the pannus, and one large subepithelial in filtrate which later ulcerated.
1281/255
their diagnostic significance. It is essential, moreover, that the EKC type of benign sub epithelial opacity should be distinguished from the trachoma "pustule" which, like the nummular opacity of nummular keratitis, tends to leave a permanent round cicatrix. None of our naturally occurring San Fran cisco cases of inclusion conjunctivitis of any age have had opacities comparable to the trachoma pustule or the necrotizing round opacity of nummular keratitis, or have de veloped gross pannus. It is still too early to tell whether any of our experimental inocu lations with inclusion conjunctivitis agents have produced permanent opacities, but no case has as yet shown gross pannus or diffuse corneal scarring. In TRIC agent studies, particularly when attempts are being made to differentiate iso lates from trachoma and inclusion conjunc tivitis, it is essential that a definitive diag nosis of the disease from which the isolate was recovered be made whenever possible. If it is possible to make only a presumptive di agnosis of either trachoma or inclusion con junctivitis, this should be so stated in the report. SUMMARY AND CONCLUSIONS
Fig. 3 (Thygeson). Trachoma of six months' duration in a Caucasian adult, showing gross pan nus extending into the pupil and two well-devel oped limbal follicles. periorly, epithelial keratitis, subepithelial infiltrates, and limbal follicles, is unequiv ocally diagnostic, but without the limbal fol licles or Herbert's pits its diagnostic value is reduced markedly. It can now be stated cat egorically that upper-quadrant micropannus alone has lost much of its diagnostic value since it is also found occasionally in nontrachomatous disease. In view of the importance ascribed by the London observers to the so-called "punctate lesions" of trachoma and inclusion conjunc tivitis, some consideration must be given to
1. The corneal changes of trachoma in Indian, Mexican and white school children have been mild but useful in making pre sumptive and definitive clinical diagnoses of trachoma. 2. In adult trachoma in which gross pan nus and conjunctival cicatrization have de veloped, no difficulty has been encountered in the differential diagnosis from adult inclusion conjunctivitis. In the early stages, however, differential diagnosis may be difficult, and repeated examination of the untreated case may be necessary. 3. The trachomatous keratitis seen in pa tients in the San Francisco area and the southwestern United States differs in no major respect from trachomatous keratitis seen in other parts of the world. 4. Gross pannus, limbal follicles, or Her-
1282/256
AMERICAN JOURNAL OF OPHTHALMOLOGY
bert's peripheral pits never have been seen in inclusion conjunctivitis in the San Fran cisco area. This applies equally to the natu rally occurring and the experimentally pro duced disease. 5. The importance of micropannus as a diagnostic sign of trachoma is lessened by its occasional occurrence in vernal catarrh, adult inclusion conjunctivitis, superior limbic keratoconjunctivitis, allergic marginal infiltration, etc.
MAY, 1967
REFERENCES
1. Jones, B. R.: Ocular syndromes of TRIC virus infection and their possible genital signifi cance. Brit J. Ven. Dis. 40:3, 1964. 2. Jones, B. R. and Collier, L. H. : Inoculation of man with inclusion blennorrhea virus. Ann. N. Y.Acad. Sci. 98:212,1962. 3. Scott, J. G. (Johannesburg, South Africa). Personal communication. 4. Thygeson, P. and Dawson, C. R.: Trachoma and follicular conjunctivitis in children. Arch. Ophth. 75:3, 1966. 5. Allen, J. H. : Inclusion blennorrhea. Am. J. Ophth. 27 :833, 1944.
STUDIES ON OCULOGENITAL T R I C AGENTS ISOLATED IN DENMARK C. H.
MORDHORST,
During the last 30 to 40 years it has been commonly agreed that trachoma is not a problem in Denmark. The diagnosis of in clusion conjunctivitis and inclusion blennorrhea has never been fully established here. Since the reports of T'ang and coworkers 1 of successful attempts to grow tra choma agents in the yolk sac of embryonated eggs, improved diagnostic techniques have been available. By means of these tech niques, special clinical and laboratory efforts have been made during the past four years to detect the presence of TRIC agent infec tions among Danish eye patients. Over this four-year period, more than 200 eye patients have been examined for a possible TRIC agent infection. Most of them were referred because of symptoms of a chronic or recurrent conjunctivitis or ker atoconjunctivitis of unknown etiology. In about 35 subjects, a clinical diagnosis of tra choma or inclusion conjunctivitis could not be ruled out at the first examination; how ever, repeated search for the presence of From the Ornithosis Department, Statens Seruminstitut, Copenhagen, Denmark. Reprint requests to: Dr. C. H. Mordhorst, Statens Seruminstitut, Amager Boulevard 80, Co penhagen, Denmark.
M.D.
conjunctival inclusion bodies, and attempts to isolate TRIC agents in eggs, were all un successful. Left were 19 individuals with a presumptive clinical diagnosis of a TRIC agent disease. Laboratory studies on con junctival scrapings from all of these pa tients, in conjunction with similar studies of genital scrapings from some of the cases, have now been completed. In addition, geni tal examinations for a TRIC agent infection among 18 individuals who were associated with the eye patients infected with TRIC agent have been carried out. The preliminary results of these investi gations were reported previously.2"4 The present paper summarizes the final results of this study of the oculogenital TRIC agent infections observed during the survey mentioned above. MATERIALS AND METHODS
Detailed descriptions of techniques em ployed have been published elsewhere,3 and only data pertinent to this presentation will be given here. Patients. A majority of patients were ex amined at the Out-Patient Clinic of the De partment of Ophthalmology, Rigshospitalet, University of Copenhagen. All the newborn