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Ocular Rosacea
OCULAR ROSACEA MARK S. J E N K I N S , M. D., S T U A R T I. B R O W N , M. D., S T E V E N L. L E M P E R T , M. AND R I C H A R D J. W E I N B E R G , M. Pittsburgh,
Rosacea is a common, chronic skin dis ease affecting flush areas of the face that include the skin, cheeks, nose, and fore head. These areas are involved with per sistent erythema, papules and often pus tules, hypertrophic sebaceous glands, and telangiectasia in varying degrees. The most advanced form of the disease is rhinophyma. Rosacea is more common in women and is usually seen between the ages of 30 and 50 years. 1 Although nu merous theories have been advanced, the cause of rosacea is still unknown. No therapy was consistently successful until Sneddon 2 in 1966 showed that tetracycline was effective, especially in the pap ular and pustular forms of the disease. Most of his patients experienced im provement for at least six months after cessation of therapy with tetracycline. Ampicillin 3 and topical erythromycin 4 have also been shown to be effective. The basis for the therapeutic response to the antibiotics is not known. 5 Ocular manifestations of rosacea main ly involve the eyelids, conjunctiva, and cornea. These include blepharitis, meibomitis, chalazia, styes, and diffusely hyperemic conjunctiva. The cornea is in volved with superior punctate epithelial erosions and is most severely involved by a peripheral vascularization, usually of the lower two-thirds of the cornea fol-
From the Department of Ophthalmology, Univer sity of Pittsburgh School of Medicine and Eye and Ear Hospital, Pittsburgh, Pennsylvania. This study was supported in part by National Institutes of Health, National Eye Institute Grant No. EY 01489. (Dr. Brown). Reprint requests to Stuart I. Brown, M.D., Depart ment of Ophthalmology, Eye and Ear Hospital, 230 Lothrop St., Pittsburgh, PA 15213. 618
D.,
D.
Pennsylvania
lowed by subepithelial infiltrates central to these vessels. Thinning of the cornea occurs either by resolution of the infil trates or by gross ulcerations. These ulcerations may eventually lead to corneal perforation. Ocular rosacea has been called a com mon disease, but its incidence in an ophthalmic population is not known. 6 Also, the frequency with which ocular rosacea's signs and symptoms are found vary widely. 7,8 Treatments for ocular ros acea have also varied widely and have been generally unsuccessful. However, two brief British reports indicated that tetracycline may improve ocular rosa cea. 2,9 A recent report 10 emphasized the clinical signs and symptoms of ocular rosacea and, additionally, showed that there were tissue-fixed antibodies and complement localized to the conjunctival epithelium in most of these severely in volved patients. Tetracycline was benefi cial in all patients treated, but did not seem to affect the almost consistent find ing of mannitol-positive Staphylococcus in the conjunctiva or eyelid. In this initial series of only 18, patients were treated with two different tetracycline regimens. Follow-up was limited because many of the patients were still in the process of being treated. We describe herein the signs and symptoms in 49 patients and we provide a more uniform approach to ther apy. S U B J E C T S AND M E T H O D S
From May 1976 to April 1978, 778 patients were referred here. Ocular ros acea was diagnosed in 49. The diagnosis of rosacea was based on the findings of telangiectasia of the nose and face and
AMERICAN JOURNAL O F OPHTHALMOLOGY 88:618-622, 1979
VOL. 88, NO. 3, PART II
OCULAR ROSACEA
one or more of the following: hypertrophic sebaceous glands, papules, pustules, and erythema of the flush areas of the face. A history was taken and an ocular examination performed on every patient. In most cases a culture of the conjunctiva and eyelid margin was obtained and, in some cases, a conjunctival biopsy. Of the 49 patients, 37 were treated with tetracycline. The first ten patients in the series were given a regimen alternating three weeks of 250 mg four times a day, with one week of no therapy. When maxi mum improvement was achieved, the daily dosage was decreased to 250 mg three times a day, and slowly tapered and stopped. The last 27 patients in the series were treated with 250 mg of tetracycline four times a day and maintained on that dosage for four weeks after maximum improvement. After this, the dosage was decreased to 250 mg a day each month and finally stopped. If symptoms re curred, the previous dosage level was resumed.
red eyes, two of decreased vision, and one of epiphora. Two complained of recurrent chalazia or styes, and 21 additional pa tients had a history of these eyelid le sions. The cutaneous findings of rosacea in these patients had a wide range of severi ty. Only eight patients had marked ery thema, numerous pustules, and telangiec tasia. In most cases, there was only mild to moderate erythema, but all had telan giectasia, hypertrophic sebaceous glands, and some pustules and papules. The ocular findings in these patients were confined to the eyelids, conjunctiva, and cornea. The most common finding was varying degrees of conjunctival hyperemia that occurred in 42 of the 49 patients. The bulbar conjunctiva was most commonly affected. Telangiectasia of the eyelid margin was found in 31 (63%) of the patients. Chalazia were also common with 11 patients affected at the time of the initial examination. One pa tient had a stye in both the upper eyelids. Numerous patients had eyelid margin notches or conjunctival scars indicative of previous chalazia. Purulent meibomitis and eyelid swelling with erythema were found in two patients; 23 patients had varying degeees of blepharitis. Corneal findings were present in 36 (74%) of the patients. Punctate epithelial erosion, usually in the inferior one-half of the cornea, was the most common find ing, with 20 patients being affected. Epi thelial microcysts, fingerprint lines, and map-like changes were seen in 17 (35%) of the patients. Six patients with intermit tent pain on awakening had characteristic signs of recurrent erosions, that is, dis crete areas of epithelial elevations, epi thelial erosions, and subepithelial opaci ties. Ten patients exhibited more severe forms of keratitis; five had marked stromal thinning and vascularization. Of the five patients, one had a descemetocele in
RESULTS
Of 778 patients examined, 49 had ocu lar rosacea, representing an incidence of 6.3%; 20 were male and 29 were female. The youngest patient was 14 years of age. The rest of the patients were between 21 and 69 years of age. Of the 49 patients, 40 had the chief complaint either of foreign body sensa tion, pain, or burning. The symptoms were usually marked and often more se vere than would be expected from the physical findings. These complaints were constant in some patients and intermit tent in others. Both eyes were affected, usually simultaneously, but occasionally alternately, and in one patient only one eye was affected with burning. Six pa tients had complaints of intermittent sharp pain, usually occurring on awaken ing in the morning. Three patients had initial complaints of
619
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AMERICAN JOURNAL OF OPHTHALMOLOGY
her only involved eye. The other four patients had vascularization and thinning of the inferior one-half of the cornea of both eyes. Eight patients had mild pe ripheral stromal thinning, vasculariza tion, and infiltrates; one of these patients had a partial ring-shaped infiltration. Two patients had peripheral nodular epithelial elevations and dense subepithelial opaci ties in one of their eyes. Of the 49 patients, 37 were treated with tetracycline and had an average follow-up of five to 42 months (average 13 months); 36 of these patients improved markedly beginning four days to three weeks after initiation of therapy. One patient did not respond and tetracycline was discontin ued after six weeks; 15 patients have remained asymptomatic since therapy was discontinued; follow-up has been from five to 28 months. Of the remaining 20 patients eight had pain or foreign body sensation or both, but had few physical findings to account for their complaints. Of the eight, five had a few punctate epithelial erosions and four had only mild to moderate conjunctival hyperemia; three of the eight were put on the initial treatment regimen and their symptoms recurred each time the tetracycline was stopped. Eventually they became refrac tory to tetracycline and the medication was discontinued. The remaining five have had significant but not complete relief from their discomfort. These patients were not able to taper their medi cations until after at least five months, without recurrence of their symptoms. Presently, three of the patients are taking 250 mg of tetracycline per day and the remaining two are taking 500 mg per day. Of the six patients with the signs and symptoms of recurrent erosions four were treated and had complete relief within two weeks after initiation of therapy. The symptoms recurred in one patient on ta pering the medication to three times a day. Increasing the medication to four
SEPTEMRER, 1979
times a day resulted in relief of symptoms once more. The therapy of the three re maining patients has been tapered to one pill a day (250 mg) without recurrence of the erosions. All patients with the more severe forms of keratitis showed improvement from four to 17 days after initiation of therapy and all healed before 28 days; four of seven patients have tapered and stopped their medication without recurrences of their original symptoms and three are taking one pill (250 mg) a day or every other day. There have been no recurrenc es of chalazion or corneal infiltration and vascularization while on therapy or after cessation. However, one patient who had severe corneal thinning in one eye devel oped a chalazion in the previously uninvolved eye one year after the medication was discontinued. Improvement of cutaneous rosacea preceded, accompanied, or followed im provement in ocular rosacea. Adverse ef fects to tetracycline occurred in five pa tients: three patients experienced mild gastrointestinal symptoms; one patient developed persistent diarrhea that was improved by an antispasmodic and reducing the daily dose of tetracycline; one patient complained of extreme drowsiness and discontinued tetracy cline. DISCUSSION 6
Duke-Elder described ocular rosacea as a common, frequently undiagnosed disease. The actual incidence in the gen eral population is unknown. Difficulty in obtaining an accurate assessment of the incidence is probably related to the rare cooperative studies between dermatolo gists and ophthalmologists. However, an incidence of 6.3% in a cornea/external disease practice where more than 50% of patients are referred for surgery, estab lishes ocular rosacea as a common exter nal disease problem. In our study it af-
VOL. 88, NO. 3, PART II fected women more commonly than men and eight patients (17%) were under 30 years of age. The signs and symptoms of ocular rosacea are generally those that are common in the everyday practice of oph thalmology, that is, burning, foreign body sensation and pain around the eyes, superficial punctate epithelial erosions, styes and chalazia, meibomitis and bleph aritis. Another common finding was mapdot subepithelial opacities (discrete gray-white dots and geographic map-like areas). These were found in 17 (35%) of the patients and have not been previously described with ocular rosacea. An associ ated and also previously undescribed finding occurred in six patients who had the typical signs and symptoms of recur rent erosions. Although we initially be lieved that these recurrent erosions were not related to the patient's cutaneous rosacea, their quick relief of symptoms from treatment with tetracycline and re currence when the dosage was reduced indicated they were somehow related. We were particularly impressed by the eight patients who bitterly complained of discomfort but who had minimal signs relating to their symptoms. These patients showed no photophobia, minimal to no tearing, a minimal amount of conjunctival hyperemia, and occasionally superficial punctate epithelial erosions. Two patients had discrete elevations in the periphery of the cornea of one eye. In one of these patients, the elevations were opaque and in the other patient they were transparent. While we were observing the patient with the transparent nodules in one eye, he developed a chalazion in the upper eyelid of his other eye. Within one week after the chalazion pointed through the tarsal con junctival area, the cornea of this eye de veloped superficial punctate opacifications in the periphery that were quickly followed by opacifications of the subep ithelial areas and later by transparent nodular elevations in the areas of subep
OCULAR ROSACEA
621
ithelial opacification. The other and more severe corneal findings in this series were typical of ocular rosacea with peripheral corneal vascularization, infiltration and corneal thinning, with the exception of one patient who had a partial ring infil trate with overlying erosions of the epi thelium. All patients except one improved be tween four days and three weeks after initiation of therapy with tetracycline. Two patients who were treated with the first regimen initially improved with tet racycline but their symptoms recurred each time the drug was stopped and, after the third cessation of tetracycline, their symptoms recurred and no longer re sponded to therapy. At this point, we changed to the second regimen for the remainder of the patients. There two pa tients were part of the group who had severe discomfort with minimal signs. The treatment of this group of patients resulted in uniform improvement, but never total loss of symptoms. Although we have been able to taper the medica tions to once a day in three patients, the rest have recurrence of symptoms with tapering of the medication, and none have been able to stop treatment at this time. The treatment of the patients with se vere corneal thinning, infiltration, and vascularization was most successful. Their corneas began healing between four to 17 days after initiation of therapy and healing was complete by three weeks in all patients. All patients but one have been able to taper and stop their medica tions without recurrence. The most commonly recommended regimen for treatment of cutaneous rosa cea is from 250 to 1,000 mg of tetracycline a day for six weeks. 1,3 Nine patients in the present series had similar treatments before their referral to us. Although their cutaneous rosacea had apparently im proved, their ocular signs and symptoms either did not improve or had recurred
622
AMERICAN JOURNAL OF OPHTHALMOLOGY
within two weeks after treatment with tetracycline was stopped. The first treat ment regimen that was used by the first ten patients was recommended by a der matologist. This regimen also proved unsuccessful for ocular rosacea. Our ex periences in this study indicate that unlike cutaneous rosacea, patients with ocular rosacea require more prolonged treatment with gradual tapering of the daily dosage of tetracycline. The reason that rosacea responds to tetracycline is unknown. Attempts at relating the cutaneous disease to the pres ence of mannitol positive Staphylococcus have been unsuccessful 5 and the recent study by us 1 0 showed that the organisms were still present on the eye lids or conjunctiva in most eyes that had responded to long-term treatment with tetracycline. However, this study 1 0 was mainly qualitative. Despite the lack of correlation of Staphylococcus with the disease and its treatment, the fact that rosacea patients respond to ampicillin 3 and topical erythromycin 4 suggests that these antibiotics are affecting some organ ism somewhere in the body. Tetracycline does not appear to have an effect on the lipid composition of themeibomian secre tions of rosacea patients 1 1 and rosacea patients do not have a difference in the lipid composition of their meibomian se cretions from apparently normal people. 1 2 SUMMARY
Ocular rosacea was diagnosed in 49 patients. The most common signs and symptoms were foreign body sensation, burning, superficial punctate erosions, chalazia, and blepharitis. Less common but dangerous to the vision was cornea! thinning, vascularization, and infiltrates.
SEPTEMBER, 1979
Three new associated symptoms were found. These were mapdot subepithelial opacities, recurrent erosions, and moder ately severe foreign body sensation, pain or burning with minimal associated signs. Of the 49 patients, 37 were treated with 250 mg of oral tetracycline four times a day, which resulted in improvement in almost all patients from four to 17 days after initiation of therapy. Most of the patients have been able to taper, or taper and stop therapy without recurrence of their symptoms. Those patients with for eign body sensation, burning, and pain required the most prolonged therapy in order to taper or stop treatment with tetra cycline. REFERENCES 1. Moschella, S. I,., Pillsbury, D. M., and Harlev, H. .].: Dermatology, vol. 2. Philadelphia, W. B. Saunders Company, 1975, pp. 1139-1142. 2. Sneddon, I. B.: A clinical trial of tetraevcline in rosacea. Br. J. Dermatol. 78:649, 1966. 3. Marks, R., and Ellis, J.: Comparative effective ness of TCN and ampicillin in rosacea. Lancet 2:1049, 1972. 4. Mills, D. H.: Topically applied erythromycin in rosacea. Arch. Dermatol. 112:553, 1976. 5. Marks, H.: Concepts in the pathogenesis of rosacea. Br. J. Dermatol. 80:170, 1968. 6. Duke-Elder, S.: Diseases of the Outer Eye. Conjunctiva. In Svsteni of Ophthalmology, vol. 8, pt. 1. St. Louis, C.'V. Mosby, 1965, p. 537. 7. Borrie, P.: Rosacea with special reference to its ocular manifestations. Br. J. Dermatol. 65:458, 1953. 8. Starr, P. A. J., and MacDonald, A.: Oculocutaneous aspects of rosacea. Proc. R. Soc. Med. 62:9, 1969. 9. Marnion, V. J. Tetraevcline in the treatment of ocular rosacea. Proc. R. Soc. Med. 62:11, 1969. 10. Brown, S. I., and Shahinian, L.: Diagnosis and treatment of ocular rosacea. Ophthalmology 85:779, 1978. 11. Pye, R. J., Meyrick, C , and Burton, J. L.: Skin surface lipid composition in rosacea. Br. J. Derma tol. 44:161, 1976. 12. Cory, C. C , Hinki. W„ Burton, J. L., and Sinister, S.: Meibomian gland secretion in the red eyes of rosacea. Br. J. Dermatol. 89:25, 1973.
Rosacea is a common, chronic skin dis ease affecting flush areas of the face that include the skin, cheeks, nose, and fore head. These areas are involved with per sistent erythema, papules and often pus tules, hypertrophic sebaceous glands, and telangiectasia in varying degrees. The most advanced form of the disease is rhinophyma. Rosacea is more common in women and is usually seen between the ages of 30 and 50 years. 1 Although nu merous theories have been advanced, the cause of rosacea is still unknown. No therapy was consistently successful until Sneddon 2 in 1966 showed that tetracycline was effective, especially in the pap ular and pustular forms of the disease. Most of his patients experienced im provement for at least six months after cessation of therapy with tetracycline. Ampicillin 3 and topical erythromycin 4 have also been shown to be effective. The basis for the therapeutic response to the antibiotics is not known. 5 Ocular manifestations of rosacea main ly involve the eyelids, conjunctiva, and cornea. These include blepharitis, meibomitis, chalazia, styes, and diffusely hyperemic conjunctiva. The cornea is in volved with superior punctate epithelial erosions and is most severely involved by a peripheral vascularization, usually of the lower two-thirds of the cornea fol-
From the Department of Ophthalmology, Univer sity of Pittsburgh School of Medicine and Eye and Ear Hospital, Pittsburgh, Pennsylvania. This study was supported in part by National Institutes of Health, National Eye Institute Grant No. EY 01489. (Dr. Brown). Reprint requests to Stuart I. Brown, M.D., Depart ment of Ophthalmology, Eye and Ear Hospital, 230 Lothrop St., Pittsburgh, PA 15213. 618
D.,
D.
Pennsylvania
lowed by subepithelial infiltrates central to these vessels. Thinning of the cornea occurs either by resolution of the infil trates or by gross ulcerations. These ulcerations may eventually lead to corneal perforation. Ocular rosacea has been called a com mon disease, but its incidence in an ophthalmic population is not known. 6 Also, the frequency with which ocular rosacea's signs and symptoms are found vary widely. 7,8 Treatments for ocular ros acea have also varied widely and have been generally unsuccessful. However, two brief British reports indicated that tetracycline may improve ocular rosa cea. 2,9 A recent report 10 emphasized the clinical signs and symptoms of ocular rosacea and, additionally, showed that there were tissue-fixed antibodies and complement localized to the conjunctival epithelium in most of these severely in volved patients. Tetracycline was benefi cial in all patients treated, but did not seem to affect the almost consistent find ing of mannitol-positive Staphylococcus in the conjunctiva or eyelid. In this initial series of only 18, patients were treated with two different tetracycline regimens. Follow-up was limited because many of the patients were still in the process of being treated. We describe herein the signs and symptoms in 49 patients and we provide a more uniform approach to ther apy. S U B J E C T S AND M E T H O D S
From May 1976 to April 1978, 778 patients were referred here. Ocular ros acea was diagnosed in 49. The diagnosis of rosacea was based on the findings of telangiectasia of the nose and face and
AMERICAN JOURNAL O F OPHTHALMOLOGY 88:618-622, 1979
VOL. 88, NO. 3, PART II
OCULAR ROSACEA
one or more of the following: hypertrophic sebaceous glands, papules, pustules, and erythema of the flush areas of the face. A history was taken and an ocular examination performed on every patient. In most cases a culture of the conjunctiva and eyelid margin was obtained and, in some cases, a conjunctival biopsy. Of the 49 patients, 37 were treated with tetracycline. The first ten patients in the series were given a regimen alternating three weeks of 250 mg four times a day, with one week of no therapy. When maxi mum improvement was achieved, the daily dosage was decreased to 250 mg three times a day, and slowly tapered and stopped. The last 27 patients in the series were treated with 250 mg of tetracycline four times a day and maintained on that dosage for four weeks after maximum improvement. After this, the dosage was decreased to 250 mg a day each month and finally stopped. If symptoms re curred, the previous dosage level was resumed.
red eyes, two of decreased vision, and one of epiphora. Two complained of recurrent chalazia or styes, and 21 additional pa tients had a history of these eyelid le sions. The cutaneous findings of rosacea in these patients had a wide range of severi ty. Only eight patients had marked ery thema, numerous pustules, and telangiec tasia. In most cases, there was only mild to moderate erythema, but all had telan giectasia, hypertrophic sebaceous glands, and some pustules and papules. The ocular findings in these patients were confined to the eyelids, conjunctiva, and cornea. The most common finding was varying degrees of conjunctival hyperemia that occurred in 42 of the 49 patients. The bulbar conjunctiva was most commonly affected. Telangiectasia of the eyelid margin was found in 31 (63%) of the patients. Chalazia were also common with 11 patients affected at the time of the initial examination. One pa tient had a stye in both the upper eyelids. Numerous patients had eyelid margin notches or conjunctival scars indicative of previous chalazia. Purulent meibomitis and eyelid swelling with erythema were found in two patients; 23 patients had varying degeees of blepharitis. Corneal findings were present in 36 (74%) of the patients. Punctate epithelial erosion, usually in the inferior one-half of the cornea, was the most common find ing, with 20 patients being affected. Epi thelial microcysts, fingerprint lines, and map-like changes were seen in 17 (35%) of the patients. Six patients with intermit tent pain on awakening had characteristic signs of recurrent erosions, that is, dis crete areas of epithelial elevations, epi thelial erosions, and subepithelial opaci ties. Ten patients exhibited more severe forms of keratitis; five had marked stromal thinning and vascularization. Of the five patients, one had a descemetocele in
RESULTS
Of 778 patients examined, 49 had ocu lar rosacea, representing an incidence of 6.3%; 20 were male and 29 were female. The youngest patient was 14 years of age. The rest of the patients were between 21 and 69 years of age. Of the 49 patients, 40 had the chief complaint either of foreign body sensa tion, pain, or burning. The symptoms were usually marked and often more se vere than would be expected from the physical findings. These complaints were constant in some patients and intermit tent in others. Both eyes were affected, usually simultaneously, but occasionally alternately, and in one patient only one eye was affected with burning. Six pa tients had complaints of intermittent sharp pain, usually occurring on awaken ing in the morning. Three patients had initial complaints of
619
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AMERICAN JOURNAL OF OPHTHALMOLOGY
her only involved eye. The other four patients had vascularization and thinning of the inferior one-half of the cornea of both eyes. Eight patients had mild pe ripheral stromal thinning, vasculariza tion, and infiltrates; one of these patients had a partial ring-shaped infiltration. Two patients had peripheral nodular epithelial elevations and dense subepithelial opaci ties in one of their eyes. Of the 49 patients, 37 were treated with tetracycline and had an average follow-up of five to 42 months (average 13 months); 36 of these patients improved markedly beginning four days to three weeks after initiation of therapy. One patient did not respond and tetracycline was discontin ued after six weeks; 15 patients have remained asymptomatic since therapy was discontinued; follow-up has been from five to 28 months. Of the remaining 20 patients eight had pain or foreign body sensation or both, but had few physical findings to account for their complaints. Of the eight, five had a few punctate epithelial erosions and four had only mild to moderate conjunctival hyperemia; three of the eight were put on the initial treatment regimen and their symptoms recurred each time the tetracycline was stopped. Eventually they became refrac tory to tetracycline and the medication was discontinued. The remaining five have had significant but not complete relief from their discomfort. These patients were not able to taper their medi cations until after at least five months, without recurrence of their symptoms. Presently, three of the patients are taking 250 mg of tetracycline per day and the remaining two are taking 500 mg per day. Of the six patients with the signs and symptoms of recurrent erosions four were treated and had complete relief within two weeks after initiation of therapy. The symptoms recurred in one patient on ta pering the medication to three times a day. Increasing the medication to four
SEPTEMRER, 1979
times a day resulted in relief of symptoms once more. The therapy of the three re maining patients has been tapered to one pill a day (250 mg) without recurrence of the erosions. All patients with the more severe forms of keratitis showed improvement from four to 17 days after initiation of therapy and all healed before 28 days; four of seven patients have tapered and stopped their medication without recurrences of their original symptoms and three are taking one pill (250 mg) a day or every other day. There have been no recurrenc es of chalazion or corneal infiltration and vascularization while on therapy or after cessation. However, one patient who had severe corneal thinning in one eye devel oped a chalazion in the previously uninvolved eye one year after the medication was discontinued. Improvement of cutaneous rosacea preceded, accompanied, or followed im provement in ocular rosacea. Adverse ef fects to tetracycline occurred in five pa tients: three patients experienced mild gastrointestinal symptoms; one patient developed persistent diarrhea that was improved by an antispasmodic and reducing the daily dose of tetracycline; one patient complained of extreme drowsiness and discontinued tetracy cline. DISCUSSION 6
Duke-Elder described ocular rosacea as a common, frequently undiagnosed disease. The actual incidence in the gen eral population is unknown. Difficulty in obtaining an accurate assessment of the incidence is probably related to the rare cooperative studies between dermatolo gists and ophthalmologists. However, an incidence of 6.3% in a cornea/external disease practice where more than 50% of patients are referred for surgery, estab lishes ocular rosacea as a common exter nal disease problem. In our study it af-
VOL. 88, NO. 3, PART II fected women more commonly than men and eight patients (17%) were under 30 years of age. The signs and symptoms of ocular rosacea are generally those that are common in the everyday practice of oph thalmology, that is, burning, foreign body sensation and pain around the eyes, superficial punctate epithelial erosions, styes and chalazia, meibomitis and bleph aritis. Another common finding was mapdot subepithelial opacities (discrete gray-white dots and geographic map-like areas). These were found in 17 (35%) of the patients and have not been previously described with ocular rosacea. An associ ated and also previously undescribed finding occurred in six patients who had the typical signs and symptoms of recur rent erosions. Although we initially be lieved that these recurrent erosions were not related to the patient's cutaneous rosacea, their quick relief of symptoms from treatment with tetracycline and re currence when the dosage was reduced indicated they were somehow related. We were particularly impressed by the eight patients who bitterly complained of discomfort but who had minimal signs relating to their symptoms. These patients showed no photophobia, minimal to no tearing, a minimal amount of conjunctival hyperemia, and occasionally superficial punctate epithelial erosions. Two patients had discrete elevations in the periphery of the cornea of one eye. In one of these patients, the elevations were opaque and in the other patient they were transparent. While we were observing the patient with the transparent nodules in one eye, he developed a chalazion in the upper eyelid of his other eye. Within one week after the chalazion pointed through the tarsal con junctival area, the cornea of this eye de veloped superficial punctate opacifications in the periphery that were quickly followed by opacifications of the subep ithelial areas and later by transparent nodular elevations in the areas of subep
OCULAR ROSACEA
621
ithelial opacification. The other and more severe corneal findings in this series were typical of ocular rosacea with peripheral corneal vascularization, infiltration and corneal thinning, with the exception of one patient who had a partial ring infil trate with overlying erosions of the epi thelium. All patients except one improved be tween four days and three weeks after initiation of therapy with tetracycline. Two patients who were treated with the first regimen initially improved with tet racycline but their symptoms recurred each time the drug was stopped and, after the third cessation of tetracycline, their symptoms recurred and no longer re sponded to therapy. At this point, we changed to the second regimen for the remainder of the patients. There two pa tients were part of the group who had severe discomfort with minimal signs. The treatment of this group of patients resulted in uniform improvement, but never total loss of symptoms. Although we have been able to taper the medica tions to once a day in three patients, the rest have recurrence of symptoms with tapering of the medication, and none have been able to stop treatment at this time. The treatment of the patients with se vere corneal thinning, infiltration, and vascularization was most successful. Their corneas began healing between four to 17 days after initiation of therapy and healing was complete by three weeks in all patients. All patients but one have been able to taper and stop their medica tions without recurrence. The most commonly recommended regimen for treatment of cutaneous rosa cea is from 250 to 1,000 mg of tetracycline a day for six weeks. 1,3 Nine patients in the present series had similar treatments before their referral to us. Although their cutaneous rosacea had apparently im proved, their ocular signs and symptoms either did not improve or had recurred
622
AMERICAN JOURNAL OF OPHTHALMOLOGY
within two weeks after treatment with tetracycline was stopped. The first treat ment regimen that was used by the first ten patients was recommended by a der matologist. This regimen also proved unsuccessful for ocular rosacea. Our ex periences in this study indicate that unlike cutaneous rosacea, patients with ocular rosacea require more prolonged treatment with gradual tapering of the daily dosage of tetracycline. The reason that rosacea responds to tetracycline is unknown. Attempts at relating the cutaneous disease to the pres ence of mannitol positive Staphylococcus have been unsuccessful 5 and the recent study by us 1 0 showed that the organisms were still present on the eye lids or conjunctiva in most eyes that had responded to long-term treatment with tetracycline. However, this study 1 0 was mainly qualitative. Despite the lack of correlation of Staphylococcus with the disease and its treatment, the fact that rosacea patients respond to ampicillin 3 and topical erythromycin 4 suggests that these antibiotics are affecting some organ ism somewhere in the body. Tetracycline does not appear to have an effect on the lipid composition of themeibomian secre tions of rosacea patients 1 1 and rosacea patients do not have a difference in the lipid composition of their meibomian se cretions from apparently normal people. 1 2 SUMMARY
Ocular rosacea was diagnosed in 49 patients. The most common signs and symptoms were foreign body sensation, burning, superficial punctate erosions, chalazia, and blepharitis. Less common but dangerous to the vision was cornea! thinning, vascularization, and infiltrates.
SEPTEMBER, 1979
Three new associated symptoms were found. These were mapdot subepithelial opacities, recurrent erosions, and moder ately severe foreign body sensation, pain or burning with minimal associated signs. Of the 49 patients, 37 were treated with 250 mg of oral tetracycline four times a day, which resulted in improvement in almost all patients from four to 17 days after initiation of therapy. Most of the patients have been able to taper, or taper and stop therapy without recurrence of their symptoms. Those patients with for eign body sensation, burning, and pain required the most prolonged therapy in order to taper or stop treatment with tetra cycline. REFERENCES 1. Moschella, S. I,., Pillsbury, D. M., and Harlev, H. .].: Dermatology, vol. 2. Philadelphia, W. B. Saunders Company, 1975, pp. 1139-1142. 2. Sneddon, I. B.: A clinical trial of tetraevcline in rosacea. Br. J. Dermatol. 78:649, 1966. 3. Marks, R., and Ellis, J.: Comparative effective ness of TCN and ampicillin in rosacea. Lancet 2:1049, 1972. 4. Mills, D. H.: Topically applied erythromycin in rosacea. Arch. Dermatol. 112:553, 1976. 5. Marks, H.: Concepts in the pathogenesis of rosacea. Br. J. Dermatol. 80:170, 1968. 6. Duke-Elder, S.: Diseases of the Outer Eye. Conjunctiva. In Svsteni of Ophthalmology, vol. 8, pt. 1. St. Louis, C.'V. Mosby, 1965, p. 537. 7. Borrie, P.: Rosacea with special reference to its ocular manifestations. Br. J. Dermatol. 65:458, 1953. 8. Starr, P. A. J., and MacDonald, A.: Oculocutaneous aspects of rosacea. Proc. R. Soc. Med. 62:9, 1969. 9. Marnion, V. J. Tetraevcline in the treatment of ocular rosacea. Proc. R. Soc. Med. 62:11, 1969. 10. Brown, S. I., and Shahinian, L.: Diagnosis and treatment of ocular rosacea. Ophthalmology 85:779, 1978. 11. Pye, R. J., Meyrick, C , and Burton, J. L.: Skin surface lipid composition in rosacea. Br. J. Derma tol. 44:161, 1976. 12. Cory, C. C , Hinki. W„ Burton, J. L., and Sinister, S.: Meibomian gland secretion in the red eyes of rosacea. Br. J. Dermatol. 89:25, 1973.