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Microbial Keratitis in Patients Infected with the Human Immunodeficiency Virus
Microbial Keratitis in Patients Infected with the Human Immunodeficiency Virus Ramzi K. Hemady, MD Background: Posterior segment complications of systemic infection with the human immunodeficiency virus (HIV) are well recognized. The anterior segment complications often are, however, overlooked. The author treated 20 episodes of nonherpetic infectious keratitis in 17 eyes of 13 patients infected with HIV who presented between August 1990 and May 1994. Methods: Review of records. Results: Nine patients were women, and four were men. Mean age was 35.2 years. The keratitis was bilateral in four patients, polymicrobial in four, and recurrent in two. The most common infecting organism was Candida albicans (5 eyes), a rare cause of keratitis in immunocompetent individuals. Other organisms included Staphylococcus aureus in four eyes, Staphylococcus epidermidis in four, Bacillus sp in two, and one each Pseudomonas aeruginosa, alpha-hemolytic Streptococcus, Micrococcus sp, and Capnocytophaga sp. Seven eyes retained 20/30 or better visual acuity after treatment, eight had visual acuity of 20/50 or worse, and two were eviscerated. Classic predisposing factors for infectious keratitis were found in only two patients and included contact lens wear and atopy in one patient each. Twelve patients had a history of intravenous drug abuse. Conclusion: Infectious keratitis should be recognized as a complication of systemic HIV infection, especially in the context of drug abuse. The prognosis for recovery of vision in these patients often is poor. Ophthalmology 1995;102:1026-1030
Infectious and noninfectious retinopathies and choroidopathies are well-recognized complications of systemic infection with the human immunodeficiency virus (HIV).1-3 Less well appreciated and recognized are the anterior segment findings in individuals infected with HIV. I report 13 patients infected with HIV and infectious keratitis. To my knowledge, this is the largest series of such patients reported. Four of these patients were included in a previous report. 4
Originally received: October 31, 1994. Revision accepted: March 2, 1995. From the Cornea Service, Department of Ophthalmology, University of Maryland School of Medicine, Baltimore. Presented in part at the Annual Meeting of the Ocular Immunology and Microbiology Group, San Francisco, 1994. Reprint requests to Ramzi K. Hemady, MD, Department of Ophthalmology, University of Maryland Hospital, 22 S. Greene St, Baltimore, MD 21201.
1026
Materials and Methods From August 1990 to May 1994, 13 patients who tested positive for HIV presented to the Ophthalmology Clinic at the University of Maryland Hospital with infectious keratitis. The records of these patients were retrieved and reviewed. Data collected included patient age, sex, race, eye involvement, culture results, treatment, final visual acuity, ocular history, HIV-infection status, review ofsysterns, and CD-4 cell counts at the time of presentation.
Selected Case Reports Case 8. A 39-year-old African-American, heterosexual man,
who was HIV-positive for 10 years, presented on September 16, 1993, with redness and discharge in the right eye of several weeks' duration. Review of systems was significant for intravenous drug abuse and smoking crack cocaine. The patient claimed, however,
Hemady . Keratitis and HIV that he had been "clean" and in drug rehabilitation for 6 years. He denied ocular trauma, contact lens wear, and use of topical ocular medications. Results of an ocular examination in 1988 showed visual acuities of 20/20 in both eyes and absence of ocular pathology. On examination, best-corrected visual acuities were 20/40 in the right eye and 20/20 in the left. Slit-lamp biomicroscopy showed a small paracentral epithelial defect with infiltrates but no stromal loss in the right eye. The remaining results of the examination were unremarkable. An infectious keratitis was suspected, and cultures were performed. Topical cefazolin sodium (50 mg/ml) and 0.3% ciprofloxacin HCI were begun hourly. The CD-4 count was 595 celis/ill. Unfortunately, the cultures were lost. The patient was lost to follow-up until December 26, 1993, when he returned without complications and having discontinued all eye drops. Results of examination showed bestcorrected visual acuities of20/20 in each eye and a small central corneal scar in the right eye. He again was lost to follow-up until May 4, 1994, when he had decreased vision, redness, and pain in the right eye. Best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left. Results of examination of the right eye showed decreased corneal sensation and two paracentral, distinct epithelial defects with infiltrates. Results of examination of the left eye were benign. An infectious keratitis was suspected, and cultures were performed. Topical cefazolin sodium (50 mg/ml) and 0.3% ciprofloxacin HCI were begun. The cultures subsequently grew Candida albicans and Staphylococcus aureus. Cefazolin and ciprofloxacin were discontinued, and 0.15% amphotericin Band trimethoprim sulfate/polymyxin B sulfate were begun, based on the culture results and sensitivities. The patient was last seen on May 9, 1994. Visual acuity in the right eye was 20/200 and the epithelial defect and infiltrates were resolving. He is lost to follow-up. Case 9. A 29-year-old African-American woman presented on May 6, 1991, with decreased vision, pain, and discharge in the right eye. She denied trauma, contact lens wear, previous ocular disease, and use of topical medications. She was an active intravenous drug abuser but denied use of crack cocaine. Results of an HIV test done 3 months previously were negative. Visual acuities were light perception in the right eye and 20/20 in the left eye. Results of examination of the right eye showed diffuse corneal inflammation with thinning. The right cornea was scraped and cultured and 0.3% ciprofloxacin, cefazolin (50 mg/ ml), and gentamicin eye drops (12 mg/ml) were begun. On May 9, 1991, the patient had severe pain in the right eye. Results of examination showed no light perception and corneal perforation; an evisceration was performed. During laboratory workup for the corneal ulcer, the patient tested positive for HIV. Thirteen days after the cultures had been obtained, Capnocytophaga sp was isolated. The patient presented again on May 31 , 1991 , with pain and redness in the left eye. Results of examination showed corneal infiltrates and an epithelial defect inferiorly. Visual acuity was 20/20. Cultures were obtained, and 0.3% ciprofloxacin HCI eye drops were begun. The cultures grew S. aureus and a coagulasenegative Staphylococcus sp. By June 6, 1991 , the corneal infiltrates and epithelial defect had resolved. The patient presented again on March 3, 1992, with pain and redness in the left eye. Results of examination showed bestcorrected visual acuity of 20/100 and two distinct areas of corneal infiltrates and epithelial defects. Cultures were performed, and 0.3% ciprofloxacin HCI eye drops were begun. A CD-4 count was less than to celis/ill. The cultures grew C. albicans, S. aureus, and alpha-hemolytic Streptococcus. Subsequently, 0.15% am-
photericin B eye drops were begun. The inferior corneal infiltrates resolved promptly. The central corneal infiltrates persisted, however, and 50 mg/ml vancomycin eye drops were started on March 18, 1992. This treatment was followed by gradual resolution ofthe central corneal infiltrates with resultant visual acuity of 20/30. On September 12, 1993, she again had redness, irritation, and discharge. Results of examination showed a central epithelial defect with infiltrates. Cultures were taken, and cefazolin (50 mg/ml) and 0.3% ciprofloxacin HCI were begun. Cultures grew S. aureus. The keratitis resolved within a few days, with residual central corneal scarring and visual acuity of 20/200. When last seen in June 1994, visual acuity in the left eye was 20/60, and the CD-4 count was 400 cellS/ill. She had been enrolled in a drug rehabilitation program for 1 year during which she was completely free of ocular problems.
Results Demographics The results are summarized in Table I. Nine (69%) patients were women, and 4 (31 %) were men. Mean age was 35.2 years (range, 21-45 years). Eleven patients were African-American, and two were white.
Keratitis Twenty episodes of keratitis developed in 17 eyes of the 13 patients reported herein. Patients typically had red and irritated eyes, decreased vision, and discharge lasting several days to several weeks. In three patients, the infection affected the corneas of both eyes simultaneously. Multiple temporally independent episodes of keratitis developed in two other patients (4 episodes in 1, 2 episodes in another). Four infections were polymicrobial. Nine episodes were located centrally in the cornea, eight were inferior, two were diffuse, and one was superior. Infecting microbes were recovered in 16 of the 20 episodes of keratitis encountered. Cultured organisms included C. albicans in five eyes, S. aureus in four, Staphylococcus epidermidis in four, Bacillus sp in two, and one each Pseudomonas aeruginosa, alpha-hemolytic Streptococcus, Micrococcus sp, and Capnocytophaga sp.
Treatment and Outcome All patients initially were treated with frequent, topical cefazolin (50 mg/ml) and tobramycin (13 mg/ml), or 0.3% ciprofloxacin. This regimen was modified, depending on the culture results. All infections due to C. albicans were treated with 0.15% amphotericin B alone or in combination with 2% miconazole or 5% natamycin topically. Visual outcome generally was poor. Only 4 (34%) of the 17 affected eyes retained 20/20 visual acuity. Three eyes retained 20/30 visual acuity, and one eye each retained 20/50, 20/60, 20/100, 20/400, and hand motions visual acuity. Visual acuity in three eyes was retained at 20/200. Two eyes were eviscerated after loss of light perception and corneal perforation: one was secondary to
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Ophthalmology
Volume 102, Number 7, July 1995
Table 1. Summary of Patient Characteristics Case No.
Age (yrs)/ Sex
Eye
Culture
1 2
33/M 37/F
OS OD
3
21/F
OU
4 5
42jF
OD OS
6 7 8
23/F 35/F 39/M
9
29/F
Pseudomonas aeruginosa C. albicans Staphylococcus epidermidis Bacillus S. epidermidis a hemolytic Streptococcus No growth Bacillus micrococcus No growth No growth No growth C. albicans Capnocytophaga Staphylococcus aureus S. epidermidis S. aureus C. albicans S. aureus S. aureus C. albicans S. epidermidis C. albicans
30/M
OS OS OD OD OD OS OS
10 11 12 13
42/ F 44/F 45/M 39/F
OS OS OD OU OU
Final Visual Acuity
HIV/AIDS
CD4 cellsh·Ll
20/30
AIDS AIDS
NA
20/200, 20/50
HIV
NA
Atopy DA
20/30 20/20
HIV
290
AIDS
NA
DA CL, homosexual
20/60 20/400 20/40 20/200
HIV HIV HIV
NA NA
595
DA DA DA
Eviscerate
HIV
NA
DA
20/20
AIDS
260
Eviscerate
20/30 20/200 20/100 HM 20/20, 20/20 20/20, 20/30
50
Ocular History One patient was a daily wear soft contact lens user who had not had previous ocular problems. Another patient had ocular atopy. The remaining II patients denied significant previous ocular history when they had their first episode of keratitis, including contact lens use, previous ocular surgery or trauma, use of topical ocular medications, or previous history suggestive of ocular infections.
Review of Systems All 13 patients were positive for HIV. One received a diagnosis of HIV infection on laboratory workup of the corneal ulcer. Seven had the acquired immune deficiency syndrome (AIDS) as defined by the Centers for Disease Control and Prevention. 5 One patient was homosexual, and the remaining 12 patients were intravenous drug abusers. Six of these patients, however, denied recent intravenous drug abuse and actively were enrolled in drug rehabilitation and methadone-treatment programs. Although five patients admitted a history of smoking crack cocaine, all denied crack cocaine use within 2 months of
1028
DA DA
10
HIV AIDS AIDS AIDS
300 23 15 4
HIV = human immunodeficiency virus; AIDS = acquired immune deficiency syndrome; OS = left eye; DA = drug abuse; OD not available; OU = both eyes; CL = contact lens; HM = hand motions.
infection with P. aeruginosa, the other was secondary to Capnocytophaga sp.
Risk Factor
DA DA DA DA =
right eye; NA =
the onset of the ocular symptoms. The CD-4 count at the time of keratitis was available in eight patients and ranged from 4 to 595 cellshd (mean, 192 cells/,ul). One patient had a history of systemic and ocular atopy. No other significant systemic findings were noted.
Discussion Cultures were positive in 16 of the 20 episodes of keratitis in this report. An infectious etiology in the remaining four episodes was presumptive and was based on the history, clinical examination, and response to antibiotics. Eight different organisms were cultured, the majority of which were gram-positive. However, the single most commonly isolated organism was C. albicans, comprising 35% of all the organisms cultured (cases 2, 8,9, 11, and 13). Fungi are an uncommon cause of keratitis in immunocompetent individuals in the northern United States, responsible for 1% of the total patients with microbial keratitis in one large series. 6 The high yield in this report, however, may not be surprising because Candida is an opportunistic organism and may cause keratitis in immunocompromised hosts. 7 ,8 Keratitis from Bacillus sp also is uncommon and usually follows trauma in rural settings. 9 "o A Bacillus organ-
Hemady . Keratitis and HIV ism was recovered from the corneas of two patients in this series. One was a daily wear soft contact lens user; neither patient had a history of trauma. The visual outcome of ocular infections with a Bacillus organism usually is poor.9 The patients reported herein, however, recovered 20/30 and 20/20 visual acuity. Another unusual cause of keratitis was encountered in case 9. A Capnocytophaga organism was isolated from the patient's first episode of keratitis. Similar to Candida, Capnocytophaga is an opportunistic pathogen causing infections in immunocompromised individuals. 4 Two of the 13 patients in this report had "classic" predisposing factors for corneal infections. These were soft contact lens wear in one patient and atopic disease in another. All 13 patients were, however, tested positive for HIV, and 12 of the 13 were drug abusers. It is possible that the co-existence of HIV infection and drug abuse may have produced an ocular surface environment conducive to the development of corneal infections in these patients. There are several mechanisms by which systemic infection with HIV may alter the defenses of the ocular surface. Lucca and colleagues reported keratoconjunctivitis sicca in 20% of men ll and 17% of women infected with HIV (Lucca JA, Farris RL. Keratoconjunctivitis sicca in HI V-positive female individuals. Abstract 2975. Presented at the 1992 ARVO Annual Meeting, Sarasota, FL). Keraconjunctivitis sicca in individuals infected with HIV was confirmed by Comerie-Smith and colleagues who, in addition, found decreased levels of lactoferrin, a protein with known antibacterial properties, in the tear film (Comerie-Smith S, Nunez J, Hosmer M, Farris RL. Tear lactoferrin levels and ocular bacterial flora in HIV positive patients. Abstract 479. Presented at the 1991 ARVO Annual Meeting, Sarasota, FL). The same investigators detected a normal lid and conjunctival microbial flora in individuals infected with HIV. However, patients infected with HIV had an increased number of microbial colonies compared with healthy control subjects. Thornberg and colleagues observed decreased blink reflexes and decreased corneal sensation in patients who tested positive for HIV, particularly those with peripheral neuropathies, regardless of CD-4 cell counts (Thornberg T, Schneiderman T, Lindquist TD. Corneal sensitivity in HIV-positive patients. Abstract 1589. Presented at the 1993 ARVO Annual Meeting, Sarasota, FL). Drug abuse also can alter the ocular surface adversely. Several recent reports,12-15 most notably by McHenry and colleagues,12 and Sachs and co-workers,15 have described the corneal findings in patients smoking crack cocaine. The terms used by the above authors to describe these eyes included the crack eye and the crack eye syndrome. Findings included corneal epithelial defects, punctate keratopathy, and sterile or infectious keratitis. These findings may be caused by a direct toxic effect of crack cocaine smoke on the corneal epithelium, decreased corneal sensation from the anesthetic effects of cocaine, chemical injuries to the corneal surface from the alkali crack cocaine, and/or mechanical rubbing of the eyes. Peyman and colleagues l6 also detected profound and rapid
analgesia after topical application of morphine but did not detect any adverse effects on the corneal epithelium. The effects of intravenous drug abuse on the ocular surface have not been studied sufficiently. 17 Incomplete lid closure during drug stupor may lead to exposure keratopathy. Although 12 of the 13 patients in this report were intravenous drug abusers, only six admitted smoking crack cocaine. These six patients, however, denied recent use of crack cocaine. Moreover, 6 of the 12 intravenous drug abusers denied recent drug abuse and were active participants in drug rehabilitation programs. The exact cause of the keratitis in these patients remains, therefore, unclear. An intriguing possibility is that the development of keratitis in patients who are in drug rehabilitation may be a marker for resumption of drug abusing behavior. It is worth noting that case 9, who had had four separate episodes of infectious keratitis involving both eyes while actively abusing drugs, has been free of keratitis since enrolling in a drug rehabilitation program. The poor outcome in many of the patients reported herein may be multifactorial. The suppressed immune responses in individuals with HIV are well known and may have been a major factor. Also, most patients presented for evaluation several weeks after the onset of symptoms, resulting in a delay in diagnosis and initiation of therapy. Compliance with medical therapy and return appointments was almost uniformly poor in these patients. This may have been due to the relative lack of pain from corneal hyposthesia and continued preoccupation with drug-seeking behavior.
References 1. Freeman WR, Lerner CW, Mines JA, et al. A prospective
2.
3. 4. 5.
6. 7. 8. 9.
study of the ophthalmologic findings in the acquired immune deficiency syndrome. Am J Ophthalmol 1984;97: 13342. Jabs DA, Green WR, Fox R, et al. Ocular manifestations of acquired immune deficiency syndrome. Ophthalmology 1989;96: 1092-9. de Smet MD, Nussenbatt [sic] RB. Ocular manifestations of AIDS. JAMA 1991 ;266:30 19-22. Aristimufio B, Nirankari VS, Hemady RK, Rodrigues MM. Spontaneous ulcerative keratitis in immunocompromised patients. Am J Ophthalmol 1993;115:202-8. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep 1992;41 (RR 17). Asbell P, Stenson S. Ulcerative keratitis: survey of 30 years' laboratory experience. Arch Ophthalmol 1982;100:77-80. Liesegang TJ. Bacterial and fungal keratitis. In: Kaufman HE, Barron BA, McDonald MB, Waltman SR, eds. The Cornea. New York: Churchill Livingstone, 1988;217-70. Koenig SB. Fungal keratitis. In: Tabbara KF, Hyndiuk RA, eds. Infections of the Eye. Boston: Little, Brown, 1986;33142. Hemady R, Zaltas M, Paton B, et al. Bacillus-induced endophthalmitis: new series of 10 cases and review of the literature. Br J Ophthalmol 1986;74:26-9.
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10. Brinser IH. Ocular bacteriology. In: Tabbara KF, Hyndiuk RA, eds. Infections of the Eye. Boston: Little, Brown, 1986; 115-50. II. Lucca lA, Farris RL, Bielroy L, Caputo AR. Keratoconjunctivitis sicca in male patients infected with human immunodeficiency virus type I. Ophthalmology 1990;97: 100810. 12. McHenry IG, Zeiter IH, Madion MP, Cowden lW. Corneal epithelial defects after smoking crack cocaine [letter]. Am J Ophthalmol 1989;108:732. 13. Strominger MB, Sachs R, Hersh PS. Microbial keratitis with crack cocaine [letter). Arch Ophthalmol 1990; I08: 1672.
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14. Zagelbaum BM, Tannenbaum MH, Hersh PS. Candida albicans corneal ulcer associated with crack cocaine [letter]. Am 1 Ophthalmol 1991; I II :248-9. 15. Sachs R, Zagelbaum BM, Hersh PS. Corneal complications associated with the use of crack cocaine. Ophthalmology 1993;100: 187-91. 16. Peyman GA, Rahimy MH, Fernandes ML. Effects of morphine on corneal sensitivity and epithelial wound healing: implications for topical ophthalmic analgesia. Bf 1 Ophthalmol 1994;78: 138-41 . 17. McLane NJ, Carroll DM. Ocular manifestations of drug abuse. Surv Ophthalmol 1986;30:298-13.
Infectious and noninfectious retinopathies and choroidopathies are well-recognized complications of systemic infection with the human immunodeficiency virus (HIV).1-3 Less well appreciated and recognized are the anterior segment findings in individuals infected with HIV. I report 13 patients infected with HIV and infectious keratitis. To my knowledge, this is the largest series of such patients reported. Four of these patients were included in a previous report. 4
Originally received: October 31, 1994. Revision accepted: March 2, 1995. From the Cornea Service, Department of Ophthalmology, University of Maryland School of Medicine, Baltimore. Presented in part at the Annual Meeting of the Ocular Immunology and Microbiology Group, San Francisco, 1994. Reprint requests to Ramzi K. Hemady, MD, Department of Ophthalmology, University of Maryland Hospital, 22 S. Greene St, Baltimore, MD 21201.
1026
Materials and Methods From August 1990 to May 1994, 13 patients who tested positive for HIV presented to the Ophthalmology Clinic at the University of Maryland Hospital with infectious keratitis. The records of these patients were retrieved and reviewed. Data collected included patient age, sex, race, eye involvement, culture results, treatment, final visual acuity, ocular history, HIV-infection status, review ofsysterns, and CD-4 cell counts at the time of presentation.
Selected Case Reports Case 8. A 39-year-old African-American, heterosexual man,
who was HIV-positive for 10 years, presented on September 16, 1993, with redness and discharge in the right eye of several weeks' duration. Review of systems was significant for intravenous drug abuse and smoking crack cocaine. The patient claimed, however,
Hemady . Keratitis and HIV that he had been "clean" and in drug rehabilitation for 6 years. He denied ocular trauma, contact lens wear, and use of topical ocular medications. Results of an ocular examination in 1988 showed visual acuities of 20/20 in both eyes and absence of ocular pathology. On examination, best-corrected visual acuities were 20/40 in the right eye and 20/20 in the left. Slit-lamp biomicroscopy showed a small paracentral epithelial defect with infiltrates but no stromal loss in the right eye. The remaining results of the examination were unremarkable. An infectious keratitis was suspected, and cultures were performed. Topical cefazolin sodium (50 mg/ml) and 0.3% ciprofloxacin HCI were begun hourly. The CD-4 count was 595 celis/ill. Unfortunately, the cultures were lost. The patient was lost to follow-up until December 26, 1993, when he returned without complications and having discontinued all eye drops. Results of examination showed bestcorrected visual acuities of20/20 in each eye and a small central corneal scar in the right eye. He again was lost to follow-up until May 4, 1994, when he had decreased vision, redness, and pain in the right eye. Best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left. Results of examination of the right eye showed decreased corneal sensation and two paracentral, distinct epithelial defects with infiltrates. Results of examination of the left eye were benign. An infectious keratitis was suspected, and cultures were performed. Topical cefazolin sodium (50 mg/ml) and 0.3% ciprofloxacin HCI were begun. The cultures subsequently grew Candida albicans and Staphylococcus aureus. Cefazolin and ciprofloxacin were discontinued, and 0.15% amphotericin Band trimethoprim sulfate/polymyxin B sulfate were begun, based on the culture results and sensitivities. The patient was last seen on May 9, 1994. Visual acuity in the right eye was 20/200 and the epithelial defect and infiltrates were resolving. He is lost to follow-up. Case 9. A 29-year-old African-American woman presented on May 6, 1991, with decreased vision, pain, and discharge in the right eye. She denied trauma, contact lens wear, previous ocular disease, and use of topical medications. She was an active intravenous drug abuser but denied use of crack cocaine. Results of an HIV test done 3 months previously were negative. Visual acuities were light perception in the right eye and 20/20 in the left eye. Results of examination of the right eye showed diffuse corneal inflammation with thinning. The right cornea was scraped and cultured and 0.3% ciprofloxacin, cefazolin (50 mg/ ml), and gentamicin eye drops (12 mg/ml) were begun. On May 9, 1991, the patient had severe pain in the right eye. Results of examination showed no light perception and corneal perforation; an evisceration was performed. During laboratory workup for the corneal ulcer, the patient tested positive for HIV. Thirteen days after the cultures had been obtained, Capnocytophaga sp was isolated. The patient presented again on May 31 , 1991 , with pain and redness in the left eye. Results of examination showed corneal infiltrates and an epithelial defect inferiorly. Visual acuity was 20/20. Cultures were obtained, and 0.3% ciprofloxacin HCI eye drops were begun. The cultures grew S. aureus and a coagulasenegative Staphylococcus sp. By June 6, 1991 , the corneal infiltrates and epithelial defect had resolved. The patient presented again on March 3, 1992, with pain and redness in the left eye. Results of examination showed bestcorrected visual acuity of 20/100 and two distinct areas of corneal infiltrates and epithelial defects. Cultures were performed, and 0.3% ciprofloxacin HCI eye drops were begun. A CD-4 count was less than to celis/ill. The cultures grew C. albicans, S. aureus, and alpha-hemolytic Streptococcus. Subsequently, 0.15% am-
photericin B eye drops were begun. The inferior corneal infiltrates resolved promptly. The central corneal infiltrates persisted, however, and 50 mg/ml vancomycin eye drops were started on March 18, 1992. This treatment was followed by gradual resolution ofthe central corneal infiltrates with resultant visual acuity of 20/30. On September 12, 1993, she again had redness, irritation, and discharge. Results of examination showed a central epithelial defect with infiltrates. Cultures were taken, and cefazolin (50 mg/ml) and 0.3% ciprofloxacin HCI were begun. Cultures grew S. aureus. The keratitis resolved within a few days, with residual central corneal scarring and visual acuity of 20/200. When last seen in June 1994, visual acuity in the left eye was 20/60, and the CD-4 count was 400 cellS/ill. She had been enrolled in a drug rehabilitation program for 1 year during which she was completely free of ocular problems.
Results Demographics The results are summarized in Table I. Nine (69%) patients were women, and 4 (31 %) were men. Mean age was 35.2 years (range, 21-45 years). Eleven patients were African-American, and two were white.
Keratitis Twenty episodes of keratitis developed in 17 eyes of the 13 patients reported herein. Patients typically had red and irritated eyes, decreased vision, and discharge lasting several days to several weeks. In three patients, the infection affected the corneas of both eyes simultaneously. Multiple temporally independent episodes of keratitis developed in two other patients (4 episodes in 1, 2 episodes in another). Four infections were polymicrobial. Nine episodes were located centrally in the cornea, eight were inferior, two were diffuse, and one was superior. Infecting microbes were recovered in 16 of the 20 episodes of keratitis encountered. Cultured organisms included C. albicans in five eyes, S. aureus in four, Staphylococcus epidermidis in four, Bacillus sp in two, and one each Pseudomonas aeruginosa, alpha-hemolytic Streptococcus, Micrococcus sp, and Capnocytophaga sp.
Treatment and Outcome All patients initially were treated with frequent, topical cefazolin (50 mg/ml) and tobramycin (13 mg/ml), or 0.3% ciprofloxacin. This regimen was modified, depending on the culture results. All infections due to C. albicans were treated with 0.15% amphotericin B alone or in combination with 2% miconazole or 5% natamycin topically. Visual outcome generally was poor. Only 4 (34%) of the 17 affected eyes retained 20/20 visual acuity. Three eyes retained 20/30 visual acuity, and one eye each retained 20/50, 20/60, 20/100, 20/400, and hand motions visual acuity. Visual acuity in three eyes was retained at 20/200. Two eyes were eviscerated after loss of light perception and corneal perforation: one was secondary to
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Ophthalmology
Volume 102, Number 7, July 1995
Table 1. Summary of Patient Characteristics Case No.
Age (yrs)/ Sex
Eye
Culture
1 2
33/M 37/F
OS OD
3
21/F
OU
4 5
42jF
OD OS
6 7 8
23/F 35/F 39/M
9
29/F
Pseudomonas aeruginosa C. albicans Staphylococcus epidermidis Bacillus S. epidermidis a hemolytic Streptococcus No growth Bacillus micrococcus No growth No growth No growth C. albicans Capnocytophaga Staphylococcus aureus S. epidermidis S. aureus C. albicans S. aureus S. aureus C. albicans S. epidermidis C. albicans
30/M
OS OS OD OD OD OS OS
10 11 12 13
42/ F 44/F 45/M 39/F
OS OS OD OU OU
Final Visual Acuity
HIV/AIDS
CD4 cellsh·Ll
20/30
AIDS AIDS
NA
20/200, 20/50
HIV
NA
Atopy DA
20/30 20/20
HIV
290
AIDS
NA
DA CL, homosexual
20/60 20/400 20/40 20/200
HIV HIV HIV
NA NA
595
DA DA DA
Eviscerate
HIV
NA
DA
20/20
AIDS
260
Eviscerate
20/30 20/200 20/100 HM 20/20, 20/20 20/20, 20/30
50
Ocular History One patient was a daily wear soft contact lens user who had not had previous ocular problems. Another patient had ocular atopy. The remaining II patients denied significant previous ocular history when they had their first episode of keratitis, including contact lens use, previous ocular surgery or trauma, use of topical ocular medications, or previous history suggestive of ocular infections.
Review of Systems All 13 patients were positive for HIV. One received a diagnosis of HIV infection on laboratory workup of the corneal ulcer. Seven had the acquired immune deficiency syndrome (AIDS) as defined by the Centers for Disease Control and Prevention. 5 One patient was homosexual, and the remaining 12 patients were intravenous drug abusers. Six of these patients, however, denied recent intravenous drug abuse and actively were enrolled in drug rehabilitation and methadone-treatment programs. Although five patients admitted a history of smoking crack cocaine, all denied crack cocaine use within 2 months of
1028
DA DA
10
HIV AIDS AIDS AIDS
300 23 15 4
HIV = human immunodeficiency virus; AIDS = acquired immune deficiency syndrome; OS = left eye; DA = drug abuse; OD not available; OU = both eyes; CL = contact lens; HM = hand motions.
infection with P. aeruginosa, the other was secondary to Capnocytophaga sp.
Risk Factor
DA DA DA DA =
right eye; NA =
the onset of the ocular symptoms. The CD-4 count at the time of keratitis was available in eight patients and ranged from 4 to 595 cellshd (mean, 192 cells/,ul). One patient had a history of systemic and ocular atopy. No other significant systemic findings were noted.
Discussion Cultures were positive in 16 of the 20 episodes of keratitis in this report. An infectious etiology in the remaining four episodes was presumptive and was based on the history, clinical examination, and response to antibiotics. Eight different organisms were cultured, the majority of which were gram-positive. However, the single most commonly isolated organism was C. albicans, comprising 35% of all the organisms cultured (cases 2, 8,9, 11, and 13). Fungi are an uncommon cause of keratitis in immunocompetent individuals in the northern United States, responsible for 1% of the total patients with microbial keratitis in one large series. 6 The high yield in this report, however, may not be surprising because Candida is an opportunistic organism and may cause keratitis in immunocompromised hosts. 7 ,8 Keratitis from Bacillus sp also is uncommon and usually follows trauma in rural settings. 9 "o A Bacillus organ-
Hemady . Keratitis and HIV ism was recovered from the corneas of two patients in this series. One was a daily wear soft contact lens user; neither patient had a history of trauma. The visual outcome of ocular infections with a Bacillus organism usually is poor.9 The patients reported herein, however, recovered 20/30 and 20/20 visual acuity. Another unusual cause of keratitis was encountered in case 9. A Capnocytophaga organism was isolated from the patient's first episode of keratitis. Similar to Candida, Capnocytophaga is an opportunistic pathogen causing infections in immunocompromised individuals. 4 Two of the 13 patients in this report had "classic" predisposing factors for corneal infections. These were soft contact lens wear in one patient and atopic disease in another. All 13 patients were, however, tested positive for HIV, and 12 of the 13 were drug abusers. It is possible that the co-existence of HIV infection and drug abuse may have produced an ocular surface environment conducive to the development of corneal infections in these patients. There are several mechanisms by which systemic infection with HIV may alter the defenses of the ocular surface. Lucca and colleagues reported keratoconjunctivitis sicca in 20% of men ll and 17% of women infected with HIV (Lucca JA, Farris RL. Keratoconjunctivitis sicca in HI V-positive female individuals. Abstract 2975. Presented at the 1992 ARVO Annual Meeting, Sarasota, FL). Keraconjunctivitis sicca in individuals infected with HIV was confirmed by Comerie-Smith and colleagues who, in addition, found decreased levels of lactoferrin, a protein with known antibacterial properties, in the tear film (Comerie-Smith S, Nunez J, Hosmer M, Farris RL. Tear lactoferrin levels and ocular bacterial flora in HIV positive patients. Abstract 479. Presented at the 1991 ARVO Annual Meeting, Sarasota, FL). The same investigators detected a normal lid and conjunctival microbial flora in individuals infected with HIV. However, patients infected with HIV had an increased number of microbial colonies compared with healthy control subjects. Thornberg and colleagues observed decreased blink reflexes and decreased corneal sensation in patients who tested positive for HIV, particularly those with peripheral neuropathies, regardless of CD-4 cell counts (Thornberg T, Schneiderman T, Lindquist TD. Corneal sensitivity in HIV-positive patients. Abstract 1589. Presented at the 1993 ARVO Annual Meeting, Sarasota, FL). Drug abuse also can alter the ocular surface adversely. Several recent reports,12-15 most notably by McHenry and colleagues,12 and Sachs and co-workers,15 have described the corneal findings in patients smoking crack cocaine. The terms used by the above authors to describe these eyes included the crack eye and the crack eye syndrome. Findings included corneal epithelial defects, punctate keratopathy, and sterile or infectious keratitis. These findings may be caused by a direct toxic effect of crack cocaine smoke on the corneal epithelium, decreased corneal sensation from the anesthetic effects of cocaine, chemical injuries to the corneal surface from the alkali crack cocaine, and/or mechanical rubbing of the eyes. Peyman and colleagues l6 also detected profound and rapid
analgesia after topical application of morphine but did not detect any adverse effects on the corneal epithelium. The effects of intravenous drug abuse on the ocular surface have not been studied sufficiently. 17 Incomplete lid closure during drug stupor may lead to exposure keratopathy. Although 12 of the 13 patients in this report were intravenous drug abusers, only six admitted smoking crack cocaine. These six patients, however, denied recent use of crack cocaine. Moreover, 6 of the 12 intravenous drug abusers denied recent drug abuse and were active participants in drug rehabilitation programs. The exact cause of the keratitis in these patients remains, therefore, unclear. An intriguing possibility is that the development of keratitis in patients who are in drug rehabilitation may be a marker for resumption of drug abusing behavior. It is worth noting that case 9, who had had four separate episodes of infectious keratitis involving both eyes while actively abusing drugs, has been free of keratitis since enrolling in a drug rehabilitation program. The poor outcome in many of the patients reported herein may be multifactorial. The suppressed immune responses in individuals with HIV are well known and may have been a major factor. Also, most patients presented for evaluation several weeks after the onset of symptoms, resulting in a delay in diagnosis and initiation of therapy. Compliance with medical therapy and return appointments was almost uniformly poor in these patients. This may have been due to the relative lack of pain from corneal hyposthesia and continued preoccupation with drug-seeking behavior.
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