- Email: [email protected]
Penetrating Keratoplasty in Herpetic Keratitis
P E N E T R A T I N G KERATOPLASTY IN H E R P E T I C KERATITIS FRANK M. POLACK, M.D.,
AND HERBERT E. KAUFMAN,
M.D.
Gainesville, Florida
The therapeutic or optical results of pene trating keratoplasty in herpetic keratitis seems to be related to the degree of ocular in flammation at the time of transplantation; however, little is known about the fate of penetrating corneal grafts in this condition. Keratoplasty in either a lamellar or penetrat ing fashion has been advised for chronic herpetic keratitis,1"10 but results have been inconsistent, probably due to a lack of differ entiation between active and inactive cases. It seemed important to study patients grafted within the last few years when new suture techniques and microsurgery could be used. In addition, the development of 5iodo-deoxyuridine (IDU) and the under standing of the pharmacology of corticoste roids were thought to markedly change the prognosis of keratoplasty in this disease so that only a recent series would be meaning ful. This paper reports the results of penetrat ing keratoplasty in 26 patients with chronic herpetic keratitis, 20 of which were clinically active and six inactive. MATERIALS AND METHODS
For descriptive purposes, our cases have been classified into active and inactive groups. Active herpetic disease has been subclassified into the following categories: epi thelial, superficial stromal (ulcerated), deep stromal (ulcerated), perforated, and perfo rated with uveitis. Avascular or moderately vascular scars in eye without activity for at least six months form the inactive group (Table 1). From the Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida. Supported in part by Public Health Ser vice Grant EY-00033 from the National Eye Insti tute. Reprint request to Frank M. Polack, M.D., De partment of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida 32601.
TABLE 1 PATIENT DATA
Status at Operation
No. No. with Im Pa proved tients Vision
Active herpetic keratitis: Stage I. Epithelial II. Stromal, superficial I I I . Stromal, deep, ulcerated IV. Perforated V. Perforated, uveitis
0 11 3 3 3
—
Totals
26
14
Inactive Scar
7 1 1 0
A total of 26 patients were studied ( 196770). Ages varied from three and one-half to 74 years of age. Diagnosis was made by a history of herpetic keratitis, by clinical ob servation, and, several cases, by virus cul tures. Eleven patients were male and 15 fe male. Severe ocular discomfort and chronic inflammation with or without perforation were the most common indications for sur gery in patients with active disease. Six pa tients were operated upon strictly for optical reasons (inactive group). The stage of the disease of our patients when operated on is shown in Table 1. In all cases, the preoperative visual acuity was between 20/80 and light perception. Except in patients under 15 years of age, all surgery was performed under local anes thesia. Preoperative medication included topical atropine, corticosteroids, and IDU in most active cases and systemic corticoste roids in two cases with uveitis. Two patients had required conjunctival flaps prior to kera toplasty because of extensive corneal disease. One patient with ulcerated keratitis devel oped a fungal ulcer and was also treated with a conjunctival flap prior to keratoplasty. Most transplants were 7.0 to 7.5 mm in di-
908
VOL. 73, NO. 6
KERATOPLASTY IN HERPETIC KERATITIS
ameter; a few were larger in size. Cataract extraction was performed in two cases at the time of keratoplasty, and, in one case, six months later. Donor tissue was either refrig erated or cryopreserved, and the suture ma terial used was 7-0 or 8-0 silk or 10-0 monofilament nylon. Postoperative treatment—Except in pa tients with severe keratouveitis who were treated with systemic corticosteroids ( started the first week postoperatively), most cases were treated symptomatically, avoiding the use of corticosteroids when possible. Iritis, not subsiding with atropine, and graft thick ening were considered indications for the use of topical dexamethasone and IDU. The corticosteroids were titrated according to the condition of the cornea, and when the reac tion subsided, a weak (0.005%) dexametha sone solution was used with IDU two or three times a day. Severe vascular reaction two or three weeks after surgery was an in dication for removal of sutures. In some in stances, all sutures were removed four weeks after surgery, but, where possible they were left for three months. Early, smooth epithelial defects in the graft without ocular inflammation were treated with patching and ointments. Epithe lial defects in the graft suggestive of rein fection were treated as herpetic epithelial in fection with IDU ointment. Virus cultures were not performed in all cases. In some, a negative culture result did not preclude the diagnosis of herpetic recurrence. If stromal disease developed in the graft, corticoste roids, topical or systemic, were added. Glau coma, when present, was treated with acetazolamide (Diamox) and oral glycerol. RESULTS
Clear grafts (Figs. 1-8) were obtained in all patients with inactive herpetic keratitis; one eye, however, developed graft rejection with opacification six months later. Of the 20 eyes with active disease, nine clear grafts were obtained (within one year). Severe re currence of herpetic keratitis and/or uveitis
909
Fig. 2 (Polack and Kaufman). Patient shown in Figure 1 one year after 7 mm penetrating kerato plasty.
occurred in 11 eyes and resulted in opaque transplants. In eyes with active disease in which clear grafts were obtained (Table 1), visual acui ties improved from light perception or finger counting to 20/60 and 20/400. Cataract, pres ent in seven of nine the eyes, accounted for the decreased visual acuity. Recurrence of herpetic keratitis occurred in four of them; two were regrafted and the other two were managed medically without permanent opaci fication but with small localized areas of edema or scarring. These two cases were re sistant to IDU and were subsequently treated with another antiviral (trifluorothymidine). Recurrence of stromal herpetic disease in the graft usually occurred within two months af ter surgery and, in many cases, a few weeks
910
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 3 (Polack and Kaufman). Recurrent ulcer ated herpetic keratitis during the active phase in a 14-year-old patient.
Fig. 4 (Polack and Kaufman). Patient shown in Figure 3 received an 8 mm penetrating grant six months later during the inactive stage. No recur rence for two years. after keratoplasty. Recurrence was charac terized by early edema of the graft, epithelial disease, stromal ulcération, deep infiltrates, and vascularization (typical dendrites were not observed). Iritis or uveitis of varying degree was always present after surgery in all active and in two inactive cases. It was modified to some extent by corticosteroids but did not preclude clear grafts. There was recurrence in 15 of the 20 active cases. Twenty-one patients had only one trans plant, whereas three had two grafts, one had three, and another had four grafts. ( T h e lat ter produced good optical and therapeutic re sults.) I n two cases (active g r o u p ) , a localized herpetic ulcération occurred in the initial
JUNE, 1972
graft that would not respond to therapy. These were treated with a conjunctival flap and regrafted when inflammation subsided, with good visual results in one case and récid iva of the graft infection in the other. In another case, the ulcer in the graft was treated with a partial flap with no récidiva during two years of follow-up ( F i g . 9 ) . Histologie examination of corneas re moved from patients with inactive corneal scars showed no evidence of inflammation. (Others, however, have reported inflamma tion in apparently inactive cases. 1 ) Diffuse round-cell infiltration and vascularization
Fig. 5 (Polack and Kaufman). Perforation in an area of recurrent stromal disease with secondary infection in a 56-year-old patient. The eye was sealed with tissue adhesive and treated medically. Later, 7 mm graft was placed in a non-inflamed eye.
Fig. 6 (Polack and Kaufman). Patient shown in Figure 5 after graft and after cataract extraction. Area of edema at six o'clock is due to iris synechiae.
VOL. 73, NO. 6
KERATOPLASTY IN HERPETIC KERATITIS
911
were present in tissues removed from eyes with deep chronic active ulcers, and severe polynuclear infiltration was found in perfo rated corneas extending to the edge of the trephination. Histologie examinations of two regraft specimens in noninflamed eyes showed defective posterior healing and a retrocorneal membrane. DISCUSSION
This study reveals that results of penetrat ing keratoplasty differ in eyes with active or inactive herpetic keratitis. The stormy post operative course and the high (75%) inci dence of herpetic recurrence in the grafts of
Fig. 7 (Polack and Kaufman). Keratoplasty for a large perforated herpetic ulcer in a 40-year-old patient. Uveitis present at the time of surgery. Clear 7.5 mm graft developed recurrence three months later and eventually opacified.
Fig. 8 (Polack and Kaufman). Recurrence of herpetic keratitis in a second graft in a 22-year-old patient who had kerato-uveitis for several years.
Fig. 9 (Polack and Kaufman). Partial conjunctival flap was used to treat area of recurrence and ulcération in graft shown one year postoperatively.
the active group are in contrast to the mild evolution seen in inactive cases. Lamellar keratoplasty has been recommended as the procedure of choice in eyes with active in flammation.4"9'11'12 Our results, however, in the past have not been satisfactory with this procedure because of vascularization, scar ring and sometimes necrosis of the lamellar graft. Nonetheless, in severely inflamed eyes with thinning or perforations, lamellar grafts may sometimes be preferred to pene trating grafts with their uncertain prognosis. It is difficult to compare our results in this series of penetrating keratoplasties with published cases because of the many factors involved, including stage, severity, and ex tension of the disease at the time of surgery. Clear keratoplasties have been obtained in 62% of operated eyes with recurrences which vary from 2413 to 40%. 14 However, recurrences were noted less frequently in older reports.1"3 It is apparent that statistics will vary greatly when results of grafting in eyes with active disease are compared to grafting done in quiet eyes. Even though our recurrence rate was 75% in active cases, 45% of the grafts survived the early recur rence. Since the herpetic disease cannot be eradicated, it is possible that more reinfec tions will eventually develop in grafted eyes at the same rate as that seen in nongrafted when followed for long periods of time.
912
AMERICAN JOURNAL OF OPHTHALMOLOGY
In inactive herpetic keratitis, only one of six grafts opacified, clinically resembling graft reaction. Recurrences of herpetic in fection have not been observed in the grafts of the inactive group followed for one year or more; however, one case showed a mild iritis which was improved with weak topical corticosteroids. Even in eyes with severe vascularization and inflammation, the inci dence of graft rejection seems to be low. No typical graft rejection was observed in the 11 cases which developed graft opacification. However, it is possible that it may have been present but difficult to elicit or separate from the picture of herpetic disease. The use of IDU in graft reinfections did not alter the corneal stromal lesions. It was helpful, however, in preventing epithelial in fections in patients with graft edema which required topical and systemic corticosteroids. It has been reported that with this combined therapy, the recurrence rate in the graft de creased from 84 to 2 4 % . " With early her petic recurrence, vascularization of the graft (with an iritis of varying degree) appeared at the site of the sutures. This necessitated re moval of the sutures, even as early as four weeks postoperatively, a procedure not with out risk because wound disruption may oc cur, particularly if corticosteroids are used. Failure of penetrating grafts in patients with active disease can be attributed to re currence of the herpetic infection, endothelial disease due to anterior segment inflam mation, and wound healing problems. The use of conjunctival flaps in herpetic corneal ulcers had also been advocated.11·12·15 Flaps may be of great value in stromal disease with iritis or uveitis because they will control ocu lar inflammation so that keratoplasty can be performed later in a quiet eye. The use of cyanoacrylate adhesives should be considered as another possibility for the temporary treatment of a perforation in acute herpetic kerato-uveitis. Penetrating keratoplasty in active stromal disease with moderate anterior segment in flammation, or inflammation controlled with
JUNE, 1972
corticosteroids, has a better prognosis. In our cases, when topical corticosteroids were used, drops were rarely used more than three or four times a day, and IDU was used along with the medication. If greater corticosteroid therapy was required, systemic corti costeroids were generally added rather than increasing the topical administration because of the great risk that topical corticosteroids carry for herpetic recurrences. Penetrating keratoplasty in active ocular herpetic disease may be required in many in stances, but the results are not so good as in inactive cases. When possible, the acute stage should be treated medically or with a conjunctival flap until the inflammation sub sides. Keratoplasty in inactive herpetic dis ease, on the other hand, offers a success rate comparable to that obtained in keratoconous or any other inactive corneal disease. SUMMARY
In 26 patients with varying degrees of ac tivity of herpetic keratitis who received pen etrating keratoplasties, the therapeutic or op tical results seemed related to the degree of ocular inflammation at the time of transplan tation. Since little is known of the fate of penetrating corneal grafts in this condition, these 26 patients were classified preoperatively as having active or inactive disease, with the active herpes cases being further divided into categories dealing with the severity of the disease. Results were then assessed ac cording to this classification. Clear grafts were obtained in all patients with inactive herpetic keratitis, while 45% of the active cases remained clear for at least one year. There were recurrences in 75% of the active cases. The stormy postoperative course and the high incidence of herpetic recurrence in the graft of the active group were in contrast to the mild evolution seen in inactive cases. ACKNOWLEDGMENTS
The following physicians referred the patients we studied : B. Bell, P. Brown, S. Clark, T. Dukes, R. Debo, G. Davidson, L. Elgin, W. Ferguson, F.
VOL. 73, NO. 6
KERATOPLASTY IN HERPETIC KERATITIS
Fischer, R. Fokes, S. Garret, L. Grace, M. Ross, C. Roehn, J. Robbins, L. Johnson, T. Kerns, W. Kum mer, A. Perana, J. Stokes, A. Updegraaf, S. Willner, and L. Wilson. We thank Mrs. Becky Bowman for her editorial assistance and J. Sewell and R. Irwin for their photographic work. REFERENCES
1. Hogan, M. J. : Corneal transplantation in the treatment of herpetic disease of the cornea. Am. J. Ophth. 43:147, 1957. 2. Ormsby, H. L. : Keratoplasty for herpetic ker atitis. Am. J. Ophth. 45:179, 1958. 3. Fine, M. : Treatment of herpetic keratitis by corneal transplantation. Am. J. Ophth. 46:671, 1958. 4. Hallerman, W. : Ergebnise der keratoplastik bei herpes. Klin. Mbl. Augenheilk. 146:161, 1965. 5. Paufique, L. : The therapeutic lamellar graft. Tr. Ophth. Soc. U. K. 69:67, 1949. 6. Franceschetti, A., and Doret, M. : Keratoplastie a chaud. Ophthalmologica 120:11, 1950. 7. Anseth, A., and Palm, E : Therapeutic keratu-
913
plasty in herpetic keratitis. Acta Ophth. 45:688, 1967. 8. Offert, G., Pouliquen, Y., and Camp, C. : L'homogreffe de la cornée dans la kératite her pétique. Arch. Opht. (Paris) 26:561, 1966. 9. Jezagabel, M., Rosazza, G, and Delaplace, M. P. : Les récidives d'herpès sur kératoplastie lamellaire. Bull. Soc. Opht. Franc. 67:759, 1967. 10. Paton, D. : Results of penetrating kerato plasty with microsurgical technique. Int. Ophth. Clin. 10:347, 1970. 11. DeVoe, A. G.: Discussion. In Boyd, B. F. (éd.) : Highlights of Ophthalmology. 5 :140, 1962. 12. Maumenee, A. E. : Discussion. In Boyd, B. F. (ed.): Highlights of Ophthalmology. 5:150, 1962. 13. Aronson, S. B., Moore, T. E., Jr., William, F. E., and Goodner, E. K. : Corticosteroids in infec tious ocular disease. In Kaufman, H. E. (ed.) : Ocular Anti-inflammatory Therapy. Springfield, Charles C Thomas, 1970, p. 20. 14. Fine, M. : Personal communication, 1971. 15. Troutman, R. : Discussion. In Boyd, B. F. (ed.) : Highlights Ophth. 5:160, 1962.
O P H T H A L M I C MINIATURE
The metallic appearance at the fundus of the eye sometimes presents coloured blood vessels, branches of the arteria centralis, which penetrate the vitreous humor ; the opacity seems to advance towards the pupil, and might be mistaken for a protruding soft cataract, an appearance which, as Mr. Saunders has remarked, is altogether delusive. In a case in which Mr. Hunter was consulted, the operation for cataract was actually under taken, and the lens being found transparent, the eye was immediately ex tirpated, from a conclusion that the disease was malignant. Benjamin Travers A Synopsis of the Diseases of the Eye and Their Treatment London, 1820, p. 219
AND HERBERT E. KAUFMAN,
M.D.
Gainesville, Florida
The therapeutic or optical results of pene trating keratoplasty in herpetic keratitis seems to be related to the degree of ocular in flammation at the time of transplantation; however, little is known about the fate of penetrating corneal grafts in this condition. Keratoplasty in either a lamellar or penetrat ing fashion has been advised for chronic herpetic keratitis,1"10 but results have been inconsistent, probably due to a lack of differ entiation between active and inactive cases. It seemed important to study patients grafted within the last few years when new suture techniques and microsurgery could be used. In addition, the development of 5iodo-deoxyuridine (IDU) and the under standing of the pharmacology of corticoste roids were thought to markedly change the prognosis of keratoplasty in this disease so that only a recent series would be meaning ful. This paper reports the results of penetrat ing keratoplasty in 26 patients with chronic herpetic keratitis, 20 of which were clinically active and six inactive. MATERIALS AND METHODS
For descriptive purposes, our cases have been classified into active and inactive groups. Active herpetic disease has been subclassified into the following categories: epi thelial, superficial stromal (ulcerated), deep stromal (ulcerated), perforated, and perfo rated with uveitis. Avascular or moderately vascular scars in eye without activity for at least six months form the inactive group (Table 1). From the Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida. Supported in part by Public Health Ser vice Grant EY-00033 from the National Eye Insti tute. Reprint request to Frank M. Polack, M.D., De partment of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida 32601.
TABLE 1 PATIENT DATA
Status at Operation
No. No. with Im Pa proved tients Vision
Active herpetic keratitis: Stage I. Epithelial II. Stromal, superficial I I I . Stromal, deep, ulcerated IV. Perforated V. Perforated, uveitis
0 11 3 3 3
—
Totals
26
14
Inactive Scar
7 1 1 0
A total of 26 patients were studied ( 196770). Ages varied from three and one-half to 74 years of age. Diagnosis was made by a history of herpetic keratitis, by clinical ob servation, and, several cases, by virus cul tures. Eleven patients were male and 15 fe male. Severe ocular discomfort and chronic inflammation with or without perforation were the most common indications for sur gery in patients with active disease. Six pa tients were operated upon strictly for optical reasons (inactive group). The stage of the disease of our patients when operated on is shown in Table 1. In all cases, the preoperative visual acuity was between 20/80 and light perception. Except in patients under 15 years of age, all surgery was performed under local anes thesia. Preoperative medication included topical atropine, corticosteroids, and IDU in most active cases and systemic corticoste roids in two cases with uveitis. Two patients had required conjunctival flaps prior to kera toplasty because of extensive corneal disease. One patient with ulcerated keratitis devel oped a fungal ulcer and was also treated with a conjunctival flap prior to keratoplasty. Most transplants were 7.0 to 7.5 mm in di-
908
VOL. 73, NO. 6
KERATOPLASTY IN HERPETIC KERATITIS
ameter; a few were larger in size. Cataract extraction was performed in two cases at the time of keratoplasty, and, in one case, six months later. Donor tissue was either refrig erated or cryopreserved, and the suture ma terial used was 7-0 or 8-0 silk or 10-0 monofilament nylon. Postoperative treatment—Except in pa tients with severe keratouveitis who were treated with systemic corticosteroids ( started the first week postoperatively), most cases were treated symptomatically, avoiding the use of corticosteroids when possible. Iritis, not subsiding with atropine, and graft thick ening were considered indications for the use of topical dexamethasone and IDU. The corticosteroids were titrated according to the condition of the cornea, and when the reac tion subsided, a weak (0.005%) dexametha sone solution was used with IDU two or three times a day. Severe vascular reaction two or three weeks after surgery was an in dication for removal of sutures. In some in stances, all sutures were removed four weeks after surgery, but, where possible they were left for three months. Early, smooth epithelial defects in the graft without ocular inflammation were treated with patching and ointments. Epithe lial defects in the graft suggestive of rein fection were treated as herpetic epithelial in fection with IDU ointment. Virus cultures were not performed in all cases. In some, a negative culture result did not preclude the diagnosis of herpetic recurrence. If stromal disease developed in the graft, corticoste roids, topical or systemic, were added. Glau coma, when present, was treated with acetazolamide (Diamox) and oral glycerol. RESULTS
Clear grafts (Figs. 1-8) were obtained in all patients with inactive herpetic keratitis; one eye, however, developed graft rejection with opacification six months later. Of the 20 eyes with active disease, nine clear grafts were obtained (within one year). Severe re currence of herpetic keratitis and/or uveitis
909
Fig. 2 (Polack and Kaufman). Patient shown in Figure 1 one year after 7 mm penetrating kerato plasty.
occurred in 11 eyes and resulted in opaque transplants. In eyes with active disease in which clear grafts were obtained (Table 1), visual acui ties improved from light perception or finger counting to 20/60 and 20/400. Cataract, pres ent in seven of nine the eyes, accounted for the decreased visual acuity. Recurrence of herpetic keratitis occurred in four of them; two were regrafted and the other two were managed medically without permanent opaci fication but with small localized areas of edema or scarring. These two cases were re sistant to IDU and were subsequently treated with another antiviral (trifluorothymidine). Recurrence of stromal herpetic disease in the graft usually occurred within two months af ter surgery and, in many cases, a few weeks
910
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 3 (Polack and Kaufman). Recurrent ulcer ated herpetic keratitis during the active phase in a 14-year-old patient.
Fig. 4 (Polack and Kaufman). Patient shown in Figure 3 received an 8 mm penetrating grant six months later during the inactive stage. No recur rence for two years. after keratoplasty. Recurrence was charac terized by early edema of the graft, epithelial disease, stromal ulcération, deep infiltrates, and vascularization (typical dendrites were not observed). Iritis or uveitis of varying degree was always present after surgery in all active and in two inactive cases. It was modified to some extent by corticosteroids but did not preclude clear grafts. There was recurrence in 15 of the 20 active cases. Twenty-one patients had only one trans plant, whereas three had two grafts, one had three, and another had four grafts. ( T h e lat ter produced good optical and therapeutic re sults.) I n two cases (active g r o u p ) , a localized herpetic ulcération occurred in the initial
JUNE, 1972
graft that would not respond to therapy. These were treated with a conjunctival flap and regrafted when inflammation subsided, with good visual results in one case and récid iva of the graft infection in the other. In another case, the ulcer in the graft was treated with a partial flap with no récidiva during two years of follow-up ( F i g . 9 ) . Histologie examination of corneas re moved from patients with inactive corneal scars showed no evidence of inflammation. (Others, however, have reported inflamma tion in apparently inactive cases. 1 ) Diffuse round-cell infiltration and vascularization
Fig. 5 (Polack and Kaufman). Perforation in an area of recurrent stromal disease with secondary infection in a 56-year-old patient. The eye was sealed with tissue adhesive and treated medically. Later, 7 mm graft was placed in a non-inflamed eye.
Fig. 6 (Polack and Kaufman). Patient shown in Figure 5 after graft and after cataract extraction. Area of edema at six o'clock is due to iris synechiae.
VOL. 73, NO. 6
KERATOPLASTY IN HERPETIC KERATITIS
911
were present in tissues removed from eyes with deep chronic active ulcers, and severe polynuclear infiltration was found in perfo rated corneas extending to the edge of the trephination. Histologie examinations of two regraft specimens in noninflamed eyes showed defective posterior healing and a retrocorneal membrane. DISCUSSION
This study reveals that results of penetrat ing keratoplasty differ in eyes with active or inactive herpetic keratitis. The stormy post operative course and the high (75%) inci dence of herpetic recurrence in the grafts of
Fig. 7 (Polack and Kaufman). Keratoplasty for a large perforated herpetic ulcer in a 40-year-old patient. Uveitis present at the time of surgery. Clear 7.5 mm graft developed recurrence three months later and eventually opacified.
Fig. 8 (Polack and Kaufman). Recurrence of herpetic keratitis in a second graft in a 22-year-old patient who had kerato-uveitis for several years.
Fig. 9 (Polack and Kaufman). Partial conjunctival flap was used to treat area of recurrence and ulcération in graft shown one year postoperatively.
the active group are in contrast to the mild evolution seen in inactive cases. Lamellar keratoplasty has been recommended as the procedure of choice in eyes with active in flammation.4"9'11'12 Our results, however, in the past have not been satisfactory with this procedure because of vascularization, scar ring and sometimes necrosis of the lamellar graft. Nonetheless, in severely inflamed eyes with thinning or perforations, lamellar grafts may sometimes be preferred to pene trating grafts with their uncertain prognosis. It is difficult to compare our results in this series of penetrating keratoplasties with published cases because of the many factors involved, including stage, severity, and ex tension of the disease at the time of surgery. Clear keratoplasties have been obtained in 62% of operated eyes with recurrences which vary from 2413 to 40%. 14 However, recurrences were noted less frequently in older reports.1"3 It is apparent that statistics will vary greatly when results of grafting in eyes with active disease are compared to grafting done in quiet eyes. Even though our recurrence rate was 75% in active cases, 45% of the grafts survived the early recur rence. Since the herpetic disease cannot be eradicated, it is possible that more reinfec tions will eventually develop in grafted eyes at the same rate as that seen in nongrafted when followed for long periods of time.
912
AMERICAN JOURNAL OF OPHTHALMOLOGY
In inactive herpetic keratitis, only one of six grafts opacified, clinically resembling graft reaction. Recurrences of herpetic in fection have not been observed in the grafts of the inactive group followed for one year or more; however, one case showed a mild iritis which was improved with weak topical corticosteroids. Even in eyes with severe vascularization and inflammation, the inci dence of graft rejection seems to be low. No typical graft rejection was observed in the 11 cases which developed graft opacification. However, it is possible that it may have been present but difficult to elicit or separate from the picture of herpetic disease. The use of IDU in graft reinfections did not alter the corneal stromal lesions. It was helpful, however, in preventing epithelial in fections in patients with graft edema which required topical and systemic corticosteroids. It has been reported that with this combined therapy, the recurrence rate in the graft de creased from 84 to 2 4 % . " With early her petic recurrence, vascularization of the graft (with an iritis of varying degree) appeared at the site of the sutures. This necessitated re moval of the sutures, even as early as four weeks postoperatively, a procedure not with out risk because wound disruption may oc cur, particularly if corticosteroids are used. Failure of penetrating grafts in patients with active disease can be attributed to re currence of the herpetic infection, endothelial disease due to anterior segment inflam mation, and wound healing problems. The use of conjunctival flaps in herpetic corneal ulcers had also been advocated.11·12·15 Flaps may be of great value in stromal disease with iritis or uveitis because they will control ocu lar inflammation so that keratoplasty can be performed later in a quiet eye. The use of cyanoacrylate adhesives should be considered as another possibility for the temporary treatment of a perforation in acute herpetic kerato-uveitis. Penetrating keratoplasty in active stromal disease with moderate anterior segment in flammation, or inflammation controlled with
JUNE, 1972
corticosteroids, has a better prognosis. In our cases, when topical corticosteroids were used, drops were rarely used more than three or four times a day, and IDU was used along with the medication. If greater corticosteroid therapy was required, systemic corti costeroids were generally added rather than increasing the topical administration because of the great risk that topical corticosteroids carry for herpetic recurrences. Penetrating keratoplasty in active ocular herpetic disease may be required in many in stances, but the results are not so good as in inactive cases. When possible, the acute stage should be treated medically or with a conjunctival flap until the inflammation sub sides. Keratoplasty in inactive herpetic dis ease, on the other hand, offers a success rate comparable to that obtained in keratoconous or any other inactive corneal disease. SUMMARY
In 26 patients with varying degrees of ac tivity of herpetic keratitis who received pen etrating keratoplasties, the therapeutic or op tical results seemed related to the degree of ocular inflammation at the time of transplan tation. Since little is known of the fate of penetrating corneal grafts in this condition, these 26 patients were classified preoperatively as having active or inactive disease, with the active herpes cases being further divided into categories dealing with the severity of the disease. Results were then assessed ac cording to this classification. Clear grafts were obtained in all patients with inactive herpetic keratitis, while 45% of the active cases remained clear for at least one year. There were recurrences in 75% of the active cases. The stormy postoperative course and the high incidence of herpetic recurrence in the graft of the active group were in contrast to the mild evolution seen in inactive cases. ACKNOWLEDGMENTS
The following physicians referred the patients we studied : B. Bell, P. Brown, S. Clark, T. Dukes, R. Debo, G. Davidson, L. Elgin, W. Ferguson, F.
VOL. 73, NO. 6
KERATOPLASTY IN HERPETIC KERATITIS
Fischer, R. Fokes, S. Garret, L. Grace, M. Ross, C. Roehn, J. Robbins, L. Johnson, T. Kerns, W. Kum mer, A. Perana, J. Stokes, A. Updegraaf, S. Willner, and L. Wilson. We thank Mrs. Becky Bowman for her editorial assistance and J. Sewell and R. Irwin for their photographic work. REFERENCES
1. Hogan, M. J. : Corneal transplantation in the treatment of herpetic disease of the cornea. Am. J. Ophth. 43:147, 1957. 2. Ormsby, H. L. : Keratoplasty for herpetic ker atitis. Am. J. Ophth. 45:179, 1958. 3. Fine, M. : Treatment of herpetic keratitis by corneal transplantation. Am. J. Ophth. 46:671, 1958. 4. Hallerman, W. : Ergebnise der keratoplastik bei herpes. Klin. Mbl. Augenheilk. 146:161, 1965. 5. Paufique, L. : The therapeutic lamellar graft. Tr. Ophth. Soc. U. K. 69:67, 1949. 6. Franceschetti, A., and Doret, M. : Keratoplastie a chaud. Ophthalmologica 120:11, 1950. 7. Anseth, A., and Palm, E : Therapeutic keratu-
913
plasty in herpetic keratitis. Acta Ophth. 45:688, 1967. 8. Offert, G., Pouliquen, Y., and Camp, C. : L'homogreffe de la cornée dans la kératite her pétique. Arch. Opht. (Paris) 26:561, 1966. 9. Jezagabel, M., Rosazza, G, and Delaplace, M. P. : Les récidives d'herpès sur kératoplastie lamellaire. Bull. Soc. Opht. Franc. 67:759, 1967. 10. Paton, D. : Results of penetrating kerato plasty with microsurgical technique. Int. Ophth. Clin. 10:347, 1970. 11. DeVoe, A. G.: Discussion. In Boyd, B. F. (éd.) : Highlights of Ophthalmology. 5 :140, 1962. 12. Maumenee, A. E. : Discussion. In Boyd, B. F. (ed.): Highlights of Ophthalmology. 5:150, 1962. 13. Aronson, S. B., Moore, T. E., Jr., William, F. E., and Goodner, E. K. : Corticosteroids in infec tious ocular disease. In Kaufman, H. E. (ed.) : Ocular Anti-inflammatory Therapy. Springfield, Charles C Thomas, 1970, p. 20. 14. Fine, M. : Personal communication, 1971. 15. Troutman, R. : Discussion. In Boyd, B. F. (ed.) : Highlights Ophth. 5:160, 1962.
O P H T H A L M I C MINIATURE
The metallic appearance at the fundus of the eye sometimes presents coloured blood vessels, branches of the arteria centralis, which penetrate the vitreous humor ; the opacity seems to advance towards the pupil, and might be mistaken for a protruding soft cataract, an appearance which, as Mr. Saunders has remarked, is altogether delusive. In a case in which Mr. Hunter was consulted, the operation for cataract was actually under taken, and the lens being found transparent, the eye was immediately ex tirpated, from a conclusion that the disease was malignant. Benjamin Travers A Synopsis of the Diseases of the Eye and Their Treatment London, 1820, p. 219