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Conjunctival Biopsy as an Aid in the Evaluation of the Patient with Suspected Sarcoidosis
Conjunctival Biopsy as an Aid in the Evaluation of the Patient with Suspected Sarcoidosis CHARLES W. NICHOLS, MD, RALPH C. EAGLE, JR., MD, MYRON YANOFF, MD, NESTOR G. MENOCAL
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Abstract: Conjunctival biopsy is an underused but simple technique in the evaluation of the patient with sarcoidosis and occasionally other systemic diseases. In 55% of patients with biopsy-proven sarcoidosis from other sites, a blind conjunctival biopsy was positive. Bilateral conjunctival biopsies and the examination of multiple sections of each biopsy were essential to obtain this high of a yield. There was no relationship between an anterior uveitis and a positive conjunctival biopsy. [Key words: conjunctival biopsy, sarcoidosis.] Ophthalmology 87:287 -291, 1980
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Conjunctival biopsy, a simple though currently underutilized procedure, is frequently helpful in the diagnosis of sarcoidosis. The efficacy of the technique in the diagnosis of sarcoid remains somewhat controversial, however. Some enthusiastic reports describe positive findings on blind biopsy in up to 33% of cases ,1-3 while others believe that this technique is helpful only when "millet-seed-like" nodules are noted clinically. 4-5 In the series reported, only patients who had blind conjunctival biopsies are included. Our results demonstrate that From the Department of Ophthalmology, School of Medicine, University of Pennsylvania, and the Hospital of the University of Pennsylvania, The Scheie Eye Institute, Presbyterian-University of Pennsylvania Medical Center, Philadelphia. Presented at the Eighty-Fourth Annual Meeting of the American Academy of Ophthalmology, San Francisco, November 5-9, 1979. Reprint requests to Charles W. Nichols, MD, Department of Ophthalmology, Hospital of the University of Pennsylvania, 3 East Gates, Philadelphia, PA 10104.
conjunctival biopsy is an extremely useful adjunct in the diagnosis of sarcoidosis provided that bilateral biopsies are performed and careful sectioning techniques are employed.
METHODS Conjunctival biopsies were performed on all patients referred to the ophthalmology service at the Hospital of the University of Pennsylvania and at the Scheie Eye Institute with the suspected diagnosis of sarcoidosis. Topical anesthesia was obtained by the instillation of multiple drops of 0.5% tetracaine hydrochloride in each inferior cul-de-sac over a IS-minute period. The lower lid was then retracted and the inferior forniceal conjunctiva was grasped with Bishop Harman forceps. With Westcott scissors, a strip of conjunctiva approximately I cm long and 0.3 cm in width was excised from each inferior cul-de-sac. Following the biopsy, the
0161-6420/80/0400/0287/$00.75 © American Academy of Ophthalmology
287
application of slight pressure for several minutes provided adequate hemostasis. No sutures or medication were required. All wounds healed without complications and no morbidity was experienced. The tissue was fixed in 10% formalin, processed in the routine manner and embedded in paraffin. At a minimum of three levels, a ribbon of 5 or 6 serial sections was routinely cut from each block (approximately 15-18 levels/ specimen). Additional sections were occasionally prepared when histologic sections revealed a suspicious degree of nongranulomatous inflammation. A biopsy was considered positive if discrete noncaseating granulomas consistent with sarcoidosis were identified.
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RESULTS One hundred and fifty patients had conjunctival biopsies performed as part of their evaluation for sarcoidosis during a four-year period. Approximately half of these were performed during the past year. "Millet-seed" conjunctival nodules were noted clinically in 4 of the 150 patients. Although these patients proved to have granulomatous conjunctivitis diagnosed at biopsy, they were excluded from the series. In 55 of the remaining 146 cases, the diagnosis of systemic sarcoid was established by transbronchial biopsy, mediastinoscopy with biopsy , liver biopsy, or biopsy of another nonocular site (Table I). Thirty of these 55 patients with nonocular biopsy-documented sarcoidosis had positive conjunctival biopsies (55%). There was no association between the presence of a conjunctival biopsy positive for sarcoidosis and intraocular involvement. An anterior uveitis was present in approximately half the patients with both positive and negative conjunctival biopsies. One patient with bilateral peripheral retinal neovascularization had negative biopsies. In the remaining 91 patients, the systemic workup for sarcoidosis including nonocular biopsies was negative. Only one of these patients had a positive conjunctival biopsy, a
granulomatous conjunctivitis secondary to Treponema pallidum. This patient had neurosyphilis and is being reported elsewhere .6 The remaining 90 patients had conjunctival biopsies negative for sarcoidosis. Subsequent follow-up has demonstrated that their systemic diagnosis was not sarcoidosis.
COMMENT This study clearly established that carefully performed conjunctival biopsy is a useful adjunct in the diagnosis of systemic sarcoidosis, (Table 1) corroborating several past studies .1-3 Although other sites may yield a greater number of positive biopsies,S biopsy of the conjunctiva is relatively simple and benign. For this reason, the conjunctiva should be the initial site of biopsy in the patient with suspected sarcoidosis. Several factors may explain the increased yield of positive biopsies in the study compared with previous reports. When possible, biopsies were routinely obtained from both inferior cul-de-sacs. In most instances, however, granulomas were found in only one specimen. Hence, bilateral biopsy alone could explain the increased yield. In addition, at least 15 sections taken from varying levels of each biopsy were prepared and examined. It was not usual to find only a single granuloma in one or two sections from one level. Hence, if only a few sections had been prepared, granulomas which were present could easily have been missed due to improper sampling of the tissue. This relatively safe and simple procedure may also have potential in the evaluation of other systemic diseases. One patient with suspected sarcoidosis was actually found to have syphilis6 on conjunctival biopsy. The role of conjunctival biopsy in the evaluation of vasculitis is currently under investigation . Simple, benign and well tolerated, conjunctival biopsy should be the initial diagnostic maneuver in the evaluation of a p. atient with suspected sarcoidosis and possible other systemic diseases. If conjunctival biopsy is performed,
Table 1. Results of Blind Conjunctival Biopsies in 146 Patients Total Patients Proven sarcoid-positive biopsy from site other than conjunctiva: Positive conjunctival biopsy (15 had uveitis) Negative conjunctival biopsy (14 had uveitis) Suspected sarCOid-systemic biopsy negative: Positive conjunctival biopsy Negative conjunctival biopsy * DiagnosiS of syphilis.
288
146 55
30 (55%) 25 (45%) 91 1* ----- (1%) 90-----(99%)
approximately half of the patients with systemic sarcoidosis will be spared more dangerous procedures such as bronchoscopy or liver biopsy. Bilateral conjunctival biopsy combined with careful histologic sampling can increase the yield of this procedure in sarcoidosis to that approaching other biopsy sites.
REFERENCES 1. Crick RP. Diagnostic conjunctival biopsy in sarcoidosis. Trans Ophthalmol Soc UK 1956; 76:403-12.
2. Bronstein JS, Frank MI, Radner OS. Conjunctival biopsy in the diagnosis of sarcoid. N Engl J Med 1962;
267:60-64. 3. Khan F, Wessely Z, Chazin SR, Serif! NS. Conjunctival biopsy in sarcoidosis. Ann Ophthalmol 1977;
9:671-76. 4. James DG. Ocular sarcoidosis. Am J Med 1959; 26331-39. 5. Israel HL, Sones M. Selection of biopsy procedures for sarcoidosis diagnosis. Arch Intern Med 1964; 113147-52. 6. Spektor FE, Eagle R, Nichols Cw. Syphilis presenting as a red eye. Submitted for publication.
Discussion by James H. Elliott, MD
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The authors have shown that blind or random conjunctival biopsies in patients who already have biopsy-proven sarcoid will be positive in 55% of cases (30 of 55). Conversely this study also shows that blind conjunctival biopsy is of no value in the diagnosis of clinical presumptive cases of sarcoid (no positives in 90 patients). The problem is, what is the value of this information to the ophthalmic practitioner? None of us are likely to be spending our time doing conjunctival biopsies on histologically proven cases of sarcoid. The important question has really not been addressed in this paper, 'which is: what is the value, if any, of a blind conjuncti val biopsy in an ocular sarcoid patient without biopsy-proven sarcoid? What the opthalmologist really wants is a simple, safe, and rapid method to corroborate histologically his clinical impression of sarcoid in patients who he is managing with suspected ocular sarcoid. This is still hard for us From the Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, TN 37232.
to obtain unless we are located in a medical center with a large sarcoid service. Sarcoid is still a difficult, evasive, and uncertain diagnosis to make. Table 1 is modified from a recent publication of Rasmussen and Neukirch. 1 It required 224 biopsies in 146 patients to yield 86 positive biopsies in 64 patients. This means that approximately 2.5 systemic biopsies must be performed to yield a positive (38% chance). What is the reliability of conjunctival biopsy? Table 2 summarizes the yield of positive conjunctival biopsies in sarcoid patients with histologically confirmed sarcoid without respect to whether it was blind or purposeful in the majority of instances. The range is 27 to 55% with a mean of 37.4%. Table 3 summarizes the major papers in the literature on the subject of the probability of a positive conjunctival biopsy in patients with presumptive clinical sarcoid. These data also, in the majority of instances, do not indicate whether the conjunctival biopsy was blind or purposeful. If the present paper is excluded, the range is 10 to 17% with a mean of 12.3%.
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Table 1. Difficulty in Tissue DiagnOSis of Sarcoid*
Biopsy Site Scalene fat pad Peripheral lymph node Mediastinal lymph node Liver Salivary gland Tonsils Muscle Skin Totals
No, Biopsies 140 2 1
Suitable Material Obtained
99
2 1
Non-caseating Granulomas Positive
Negative
51 1
48
1
71 70 30 2 2 2 4 4 o 2 2 1 2 o 2 224 182 86 86 Positive biopsies from 64 of 146 Patients (43.8% Yield)
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* Modified from: Rasmussen SM, Neukirch F. Acta Med Scand 1976; 199:209-16.
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Table 2. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid in Biopsy-proven Sarcoid
Table 3. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid in Presumptive Clinical Sarcoid
No. Patients
No . Positive
Percent
No . Patients
No. Positive
Percent
34 43 52 65 60 55*
12 16 14
35 37 27
3 4 2
10 ""10 17
20 30
33 55
29 36 12 5 91*
Author Crick 2 Crick et al 4 Bornstein et al 3 Karma et al S Kahn et al 6 Nichols et al NS = not stated; " blind. "
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Author Crick 2 Crick et al 4 Bornstein et aP Karma et al s Nichols et al
NS
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Table 4. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid: Random or "Blind" Biopsies only in Biopsy-proven and/or Presumptive Cases of Sarcoid
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15 20
50 47
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4 42 1 3
= first
NS
3 9 1* 3*
75 21 100 100
histologic evidence of sarcoid.
Table 4 summarizes the major available literature of the yield of random or "blind" biopsies in cases of biopsy proven and/or presumptive cas es of sarcoidosis . Excluding small series the range is 0 to 7% with a mean of 3% . Table 5 summarizes the major literature available on the yield of purposeful conjunctival biopsies of suspected conjunctival lesions in biopsy-proven and/or presumptive cases of sarcoid. Once again if minor series are excluded the range is 21 to 50% with a mean of about 40%. Historically it is interesting to note the conflicting opinions in the literature regarding blind and purposeful conjunctival biopsies. In 1956, Crick 2 wrote "conjunctiva without follicles will in our experience
290
33
NS
Percent
first histologic evidence of sarcoid.
Author Crick 2 Crick et al 4 Bornstein et aP Israel et al 9 Karma et al s Fulton et alB Vanderbilt (Unpublished) NS
No. Positive
36
Table 5. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid: Purposeful Biopsy of Conjunctival Lesion in Biopsy-proven and/or Presumptive Cases of Sarcoid
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fail to show sarcoid lesions." Six years later Bornstein et aP expressed a radically different view-' 'In the absence of conjunctiv al follicles on slit lamp examination, we believe that random biopsy should be performed since we have recovered noncaseating granulomas on several occasions in this manner. " The truth must lie between these opposing viewpoints. Nichols and coworkers' data have an all or none quality that cannot be substantiated by the literature, eg, a high percentage of " blind" conjunctival biopsies will be positive in biopsy-proven case s and exclusively negative in patients with presumptive sarcoid. Also the present paper does not help us develop rational guidelines for when a conjunctival biopsy should be performed. Therefore, I will make the following recommendation s for the ophthalmologist managing a patient with ocular sarcoid in regard to conjunctival biopsy . 1. It is superfluous to do a " blind " conjunctival biopsy in patients with biopsy-proven sarcoid. 2. It is superfluous to do a purposeful conjunctival biopsy in patients with biopsy-proven sarcoid unless one is trying to rule out advent of a new disease (eg, lymphoma, etc) . 3. Perform a purposeful biopsy of the conjunctiva if a suspicious lesion is discerned in all patients with clinical presumptive sarcoid. 4. Perform a blind biopsy of the conjunctiva in all patients with clinically presumptive sarcoid.
There is general agreement in the literature, and as the authors emphasize, for more conjunctival biopsies. Conjunctival biopsies are simple, safe, and do not require hospitalization. They may be more spe-
cific even though less sensitive than other more inaccessible biopsy sites. ]t is still not known whether or how much topical and systemic corticosteroids affect the biopsy results. If possible these medications should be withheld for a reasonable time period prior to conjunctival biopsy. At present, logic and evidence dictate that conjunctival biopsy (blind or purposeful) should be carried out as a first step in the diagnosis of sarcoid before other more invasive biopsy procedures are performed. REFERENCES 1. Rasmussen SM, Neukirch F. Sarcoidosis. Acta Med Scand 1976; 199:209-16. 2. Crick RP . Diagnostic conjunctival biop sy in sarcoidosis. Trans Ophthalmol Soc UK 1956; 76:403-12.
3. Bornstein JS , Frank MI, Radner DB. Conjunctival biopsy in the diagnosis of sarcoid. N Engl J Med 1962;
267 :60-4. 4. Crick RP, Hoyle C, Saville H. Eyes in sarcoidosis. Br J Ophthalmol 1961; 45:461-81. 5. Karma A, Sutinen S. Conjunctival biopsy in sarcoidosis. Acta Ophthalmol (suppl) 1975; 125:52-3. 6. Kahn F, Wessely Z. Seiff N. Conjunctival biopsy in sarcoidosis . Ann Ophthalmol 1977; 9:671-76. 7. Fong JF, Israel Cw. Conjunctival biopsy in the diagnosis of sarcoid. South Med J 1979; 72 :124-26. 8. Fulton A, Jampol L, Albert OM. Gastrointestinal sarcoidosis diagnosed by conjunctival biopsy. Am J Ophthalmol 1976; 82: 102-4. 9. Israel HL. Sones M. Selection of biopsy procedures for sarcoidosis diagnosis . Arch Intern Med 1964;
113:255-60.
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Abstract: Conjunctival biopsy is an underused but simple technique in the evaluation of the patient with sarcoidosis and occasionally other systemic diseases. In 55% of patients with biopsy-proven sarcoidosis from other sites, a blind conjunctival biopsy was positive. Bilateral conjunctival biopsies and the examination of multiple sections of each biopsy were essential to obtain this high of a yield. There was no relationship between an anterior uveitis and a positive conjunctival biopsy. [Key words: conjunctival biopsy, sarcoidosis.] Ophthalmology 87:287 -291, 1980
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Conjunctival biopsy, a simple though currently underutilized procedure, is frequently helpful in the diagnosis of sarcoidosis. The efficacy of the technique in the diagnosis of sarcoid remains somewhat controversial, however. Some enthusiastic reports describe positive findings on blind biopsy in up to 33% of cases ,1-3 while others believe that this technique is helpful only when "millet-seed-like" nodules are noted clinically. 4-5 In the series reported, only patients who had blind conjunctival biopsies are included. Our results demonstrate that From the Department of Ophthalmology, School of Medicine, University of Pennsylvania, and the Hospital of the University of Pennsylvania, The Scheie Eye Institute, Presbyterian-University of Pennsylvania Medical Center, Philadelphia. Presented at the Eighty-Fourth Annual Meeting of the American Academy of Ophthalmology, San Francisco, November 5-9, 1979. Reprint requests to Charles W. Nichols, MD, Department of Ophthalmology, Hospital of the University of Pennsylvania, 3 East Gates, Philadelphia, PA 10104.
conjunctival biopsy is an extremely useful adjunct in the diagnosis of sarcoidosis provided that bilateral biopsies are performed and careful sectioning techniques are employed.
METHODS Conjunctival biopsies were performed on all patients referred to the ophthalmology service at the Hospital of the University of Pennsylvania and at the Scheie Eye Institute with the suspected diagnosis of sarcoidosis. Topical anesthesia was obtained by the instillation of multiple drops of 0.5% tetracaine hydrochloride in each inferior cul-de-sac over a IS-minute period. The lower lid was then retracted and the inferior forniceal conjunctiva was grasped with Bishop Harman forceps. With Westcott scissors, a strip of conjunctiva approximately I cm long and 0.3 cm in width was excised from each inferior cul-de-sac. Following the biopsy, the
0161-6420/80/0400/0287/$00.75 © American Academy of Ophthalmology
287
application of slight pressure for several minutes provided adequate hemostasis. No sutures or medication were required. All wounds healed without complications and no morbidity was experienced. The tissue was fixed in 10% formalin, processed in the routine manner and embedded in paraffin. At a minimum of three levels, a ribbon of 5 or 6 serial sections was routinely cut from each block (approximately 15-18 levels/ specimen). Additional sections were occasionally prepared when histologic sections revealed a suspicious degree of nongranulomatous inflammation. A biopsy was considered positive if discrete noncaseating granulomas consistent with sarcoidosis were identified.
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RESULTS One hundred and fifty patients had conjunctival biopsies performed as part of their evaluation for sarcoidosis during a four-year period. Approximately half of these were performed during the past year. "Millet-seed" conjunctival nodules were noted clinically in 4 of the 150 patients. Although these patients proved to have granulomatous conjunctivitis diagnosed at biopsy, they were excluded from the series. In 55 of the remaining 146 cases, the diagnosis of systemic sarcoid was established by transbronchial biopsy, mediastinoscopy with biopsy , liver biopsy, or biopsy of another nonocular site (Table I). Thirty of these 55 patients with nonocular biopsy-documented sarcoidosis had positive conjunctival biopsies (55%). There was no association between the presence of a conjunctival biopsy positive for sarcoidosis and intraocular involvement. An anterior uveitis was present in approximately half the patients with both positive and negative conjunctival biopsies. One patient with bilateral peripheral retinal neovascularization had negative biopsies. In the remaining 91 patients, the systemic workup for sarcoidosis including nonocular biopsies was negative. Only one of these patients had a positive conjunctival biopsy, a
granulomatous conjunctivitis secondary to Treponema pallidum. This patient had neurosyphilis and is being reported elsewhere .6 The remaining 90 patients had conjunctival biopsies negative for sarcoidosis. Subsequent follow-up has demonstrated that their systemic diagnosis was not sarcoidosis.
COMMENT This study clearly established that carefully performed conjunctival biopsy is a useful adjunct in the diagnosis of systemic sarcoidosis, (Table 1) corroborating several past studies .1-3 Although other sites may yield a greater number of positive biopsies,S biopsy of the conjunctiva is relatively simple and benign. For this reason, the conjunctiva should be the initial site of biopsy in the patient with suspected sarcoidosis. Several factors may explain the increased yield of positive biopsies in the study compared with previous reports. When possible, biopsies were routinely obtained from both inferior cul-de-sacs. In most instances, however, granulomas were found in only one specimen. Hence, bilateral biopsy alone could explain the increased yield. In addition, at least 15 sections taken from varying levels of each biopsy were prepared and examined. It was not usual to find only a single granuloma in one or two sections from one level. Hence, if only a few sections had been prepared, granulomas which were present could easily have been missed due to improper sampling of the tissue. This relatively safe and simple procedure may also have potential in the evaluation of other systemic diseases. One patient with suspected sarcoidosis was actually found to have syphilis6 on conjunctival biopsy. The role of conjunctival biopsy in the evaluation of vasculitis is currently under investigation . Simple, benign and well tolerated, conjunctival biopsy should be the initial diagnostic maneuver in the evaluation of a p. atient with suspected sarcoidosis and possible other systemic diseases. If conjunctival biopsy is performed,
Table 1. Results of Blind Conjunctival Biopsies in 146 Patients Total Patients Proven sarcoid-positive biopsy from site other than conjunctiva: Positive conjunctival biopsy (15 had uveitis) Negative conjunctival biopsy (14 had uveitis) Suspected sarCOid-systemic biopsy negative: Positive conjunctival biopsy Negative conjunctival biopsy * DiagnosiS of syphilis.
288
146 55
30 (55%) 25 (45%) 91 1* ----- (1%) 90-----(99%)
approximately half of the patients with systemic sarcoidosis will be spared more dangerous procedures such as bronchoscopy or liver biopsy. Bilateral conjunctival biopsy combined with careful histologic sampling can increase the yield of this procedure in sarcoidosis to that approaching other biopsy sites.
REFERENCES 1. Crick RP. Diagnostic conjunctival biopsy in sarcoidosis. Trans Ophthalmol Soc UK 1956; 76:403-12.
2. Bronstein JS, Frank MI, Radner OS. Conjunctival biopsy in the diagnosis of sarcoid. N Engl J Med 1962;
267:60-64. 3. Khan F, Wessely Z, Chazin SR, Serif! NS. Conjunctival biopsy in sarcoidosis. Ann Ophthalmol 1977;
9:671-76. 4. James DG. Ocular sarcoidosis. Am J Med 1959; 26331-39. 5. Israel HL, Sones M. Selection of biopsy procedures for sarcoidosis diagnosis. Arch Intern Med 1964; 113147-52. 6. Spektor FE, Eagle R, Nichols Cw. Syphilis presenting as a red eye. Submitted for publication.
Discussion by James H. Elliott, MD
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The authors have shown that blind or random conjunctival biopsies in patients who already have biopsy-proven sarcoid will be positive in 55% of cases (30 of 55). Conversely this study also shows that blind conjunctival biopsy is of no value in the diagnosis of clinical presumptive cases of sarcoid (no positives in 90 patients). The problem is, what is the value of this information to the ophthalmic practitioner? None of us are likely to be spending our time doing conjunctival biopsies on histologically proven cases of sarcoid. The important question has really not been addressed in this paper, 'which is: what is the value, if any, of a blind conjuncti val biopsy in an ocular sarcoid patient without biopsy-proven sarcoid? What the opthalmologist really wants is a simple, safe, and rapid method to corroborate histologically his clinical impression of sarcoid in patients who he is managing with suspected ocular sarcoid. This is still hard for us From the Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, TN 37232.
to obtain unless we are located in a medical center with a large sarcoid service. Sarcoid is still a difficult, evasive, and uncertain diagnosis to make. Table 1 is modified from a recent publication of Rasmussen and Neukirch. 1 It required 224 biopsies in 146 patients to yield 86 positive biopsies in 64 patients. This means that approximately 2.5 systemic biopsies must be performed to yield a positive (38% chance). What is the reliability of conjunctival biopsy? Table 2 summarizes the yield of positive conjunctival biopsies in sarcoid patients with histologically confirmed sarcoid without respect to whether it was blind or purposeful in the majority of instances. The range is 27 to 55% with a mean of 37.4%. Table 3 summarizes the major papers in the literature on the subject of the probability of a positive conjunctival biopsy in patients with presumptive clinical sarcoid. These data also, in the majority of instances, do not indicate whether the conjunctival biopsy was blind or purposeful. If the present paper is excluded, the range is 10 to 17% with a mean of 12.3%.
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Table 1. Difficulty in Tissue DiagnOSis of Sarcoid*
Biopsy Site Scalene fat pad Peripheral lymph node Mediastinal lymph node Liver Salivary gland Tonsils Muscle Skin Totals
No, Biopsies 140 2 1
Suitable Material Obtained
99
2 1
Non-caseating Granulomas Positive
Negative
51 1
48
1
71 70 30 2 2 2 4 4 o 2 2 1 2 o 2 224 182 86 86 Positive biopsies from 64 of 146 Patients (43.8% Yield)
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* Modified from: Rasmussen SM, Neukirch F. Acta Med Scand 1976; 199:209-16.
289
Table 2. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid in Biopsy-proven Sarcoid
Table 3. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid in Presumptive Clinical Sarcoid
No. Patients
No . Positive
Percent
No . Patients
No. Positive
Percent
34 43 52 65 60 55*
12 16 14
35 37 27
3 4 2
10 ""10 17
20 30
33 55
29 36 12 5 91*
Author Crick 2 Crick et al 4 Bornstein et al 3 Karma et al S Kahn et al 6 Nichols et al NS = not stated; " blind. "
*
NS
Author Crick 2 Crick et al 4 Bornstein et aP Karma et al s Nichols et al
NS
0
1t
NS = not stated ; • all biopsies of the conjunctiva were "blind " ; t = granuloma in conjunctival biopsy associated with spirochetes .
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Table 4. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid: Random or "Blind" Biopsies only in Biopsy-proven and/or Presumptive Cases of Sarcoid
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No . Patients
No . Positive
Percent
30 43
15 20
50 47
NS
4 42 1 3
= first
NS
3 9 1* 3*
75 21 100 100
histologic evidence of sarcoid.
Table 4 summarizes the major available literature of the yield of random or "blind" biopsies in cases of biopsy proven and/or presumptive cas es of sarcoidosis . Excluding small series the range is 0 to 7% with a mean of 3% . Table 5 summarizes the major literature available on the yield of purposeful conjunctival biopsies of suspected conjunctival lesions in biopsy-proven and/or presumptive cases of sarcoid. Once again if minor series are excluded the range is 21 to 50% with a mean of about 40%. Historically it is interesting to note the conflicting opinions in the literature regarding blind and purposeful conjunctival biopsies. In 1956, Crick 2 wrote "conjunctiva without follicles will in our experience
290
33
NS
Percent
first histologic evidence of sarcoid.
Author Crick 2 Crick et al 4 Bornstein et aP Israel et al 9 Karma et al s Fulton et alB Vanderbilt (Unpublished) NS
No. Positive
36
Table 5. Yield of Conjunctival Biopsy in the Diagnosis of Sarcoid: Purposeful Biopsy of Conjunctival Lesion in Biopsy-proven and/or Presumptive Cases of Sarcoid
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fail to show sarcoid lesions." Six years later Bornstein et aP expressed a radically different view-' 'In the absence of conjunctiv al follicles on slit lamp examination, we believe that random biopsy should be performed since we have recovered noncaseating granulomas on several occasions in this manner. " The truth must lie between these opposing viewpoints. Nichols and coworkers' data have an all or none quality that cannot be substantiated by the literature, eg, a high percentage of " blind" conjunctival biopsies will be positive in biopsy-proven case s and exclusively negative in patients with presumptive sarcoid. Also the present paper does not help us develop rational guidelines for when a conjunctival biopsy should be performed. Therefore, I will make the following recommendation s for the ophthalmologist managing a patient with ocular sarcoid in regard to conjunctival biopsy . 1. It is superfluous to do a " blind " conjunctival biopsy in patients with biopsy-proven sarcoid. 2. It is superfluous to do a purposeful conjunctival biopsy in patients with biopsy-proven sarcoid unless one is trying to rule out advent of a new disease (eg, lymphoma, etc) . 3. Perform a purposeful biopsy of the conjunctiva if a suspicious lesion is discerned in all patients with clinical presumptive sarcoid. 4. Perform a blind biopsy of the conjunctiva in all patients with clinically presumptive sarcoid.
There is general agreement in the literature, and as the authors emphasize, for more conjunctival biopsies. Conjunctival biopsies are simple, safe, and do not require hospitalization. They may be more spe-
cific even though less sensitive than other more inaccessible biopsy sites. ]t is still not known whether or how much topical and systemic corticosteroids affect the biopsy results. If possible these medications should be withheld for a reasonable time period prior to conjunctival biopsy. At present, logic and evidence dictate that conjunctival biopsy (blind or purposeful) should be carried out as a first step in the diagnosis of sarcoid before other more invasive biopsy procedures are performed. REFERENCES 1. Rasmussen SM, Neukirch F. Sarcoidosis. Acta Med Scand 1976; 199:209-16. 2. Crick RP . Diagnostic conjunctival biop sy in sarcoidosis. Trans Ophthalmol Soc UK 1956; 76:403-12.
3. Bornstein JS , Frank MI, Radner DB. Conjunctival biopsy in the diagnosis of sarcoid. N Engl J Med 1962;
267 :60-4. 4. Crick RP, Hoyle C, Saville H. Eyes in sarcoidosis. Br J Ophthalmol 1961; 45:461-81. 5. Karma A, Sutinen S. Conjunctival biopsy in sarcoidosis. Acta Ophthalmol (suppl) 1975; 125:52-3. 6. Kahn F, Wessely Z. Seiff N. Conjunctival biopsy in sarcoidosis . Ann Ophthalmol 1977; 9:671-76. 7. Fong JF, Israel Cw. Conjunctival biopsy in the diagnosis of sarcoid. South Med J 1979; 72 :124-26. 8. Fulton A, Jampol L, Albert OM. Gastrointestinal sarcoidosis diagnosed by conjunctival biopsy. Am J Ophthalmol 1976; 82: 102-4. 9. Israel HL. Sones M. Selection of biopsy procedures for sarcoidosis diagnosis . Arch Intern Med 1964;
113:255-60.
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