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Prevalence of Dry Eye Among the Elderly
Prevalence of Dry Eye Among the Elderly OLIVER D. SCHEIN, MD, MPH, BEATRIZ MUNOZ, MS, JAMES M. TIELSCH, PHD, KAREN BANDEEN-ROCHE, PHD, AND SHEILA WEST, PHD
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PRODUCTS PRODUCTS AND AND SERVICES SERVICES • PURPOSE: To study the demographics and esti mate the prevalence of dry eye among elderly Americans. PRODUCTS AND population-based SERVICES CONSIDEREDprevalence TO BE OF IN. • NEW METHODS: NEW PRODUCTSAAND SERVICES CONSIDERED TO BE OF IN. terest to our readers are described on the of 2,520 residents of basis Salis study wasto performed terest our readersinare described on the basis of information supplied by the companies cited. Publication years andcited. older as of bury, Maryland, agedby 65 information supplied the companies Publication of these notices does not imply endorsement or warranty of these notices doesThe not imply endorsement warranty September 1993. population was or derived by The Ophthalmic Publishing Company, publishers of by The Publishing Company, publishers of the Ophthalmic Health Care Financing Administration from the AMERICAN JOURNAL OF OPHTHALMOLOGY, for these the AMERICAN JOURNAL OF OPHTHALMOLOGY, for these Medicare database. After completing a standard products and services. products and services. ized questionnaire pertaining to dry eye symp toms, 2,420 subjects underwent Schirmer and rose bengal tests and anatomic assessment of the meibomian glands. • RESULTS: In this population, 14.6% (363/ 2,482) were symptomatic, denned as reporting one or more drySURGICAL eye symptoms often or all the time; SURGICAL INSTRUMENTS INSTRUMENTS 2.2% (53/2,448) were symptomatic and had a low Schirmer test result (^5 mm), and 2% (48/2,432) were symptomatic and had a high rose bengal test score (^5). Furthermore, 3.5% (84/2,425) were symptomatic and had either a low Schirmer score or a high rose bengal score, and 0.7% (17/2,420) were symptomatic and had both a low Schirmer score and a high rose bengal score. No association of symptoms or signs was seen with age, sex, or race. Although anatomic features of meibomianitis were associated with the presence of symptoms (P = .01), 76% (67/88) of the individuals with
• Visitec Company, 7575 Commerce Court, Sarasota, • Visitec Company, 7575 Commerce Court, Sarasota, FLA 34243; telephone: (800) 237-2174 or (940 FLA for34243; telephone: or (940 Accepted publication May 7,705-2525 1997. (800) 237-2174 359-9883; fax: (800) Company intro359-9883; fax: (800) 705-2525Visitec Visitec Company introFrom the Department of Ophthalmology (Drs Schein, Tielsch, and duces 5216 Department LASIK Flap Irrigator Health (Vidaurri), which West, and the Ms Muftoz), of International (Dr Tielsch), duces the 5216 LASIK Flap Irrigator (Vidaurri), which and Department Biostatistics Bandeen-Roche), The Johns Hop45 features two of parallel .50 x(Dr 13-mm tip extensions angled two parallelMaryland. .50 x 13-mm tipbyextensions angled 45 kinsfeatures University, Baltimore, Supported grant PO1AG10184 degrees and placed 1 mm apart. Each extension possesses fromdegrees the National Bethesda, Maryland. Data from this andInstitute placedof1Aging, mm apart. Each extension possesses fourwere ports, twoin inside twomeeting outside. universal study presented at theand annual of the The Association for four ports, two part inside and two outside. The universal Research in Vision and Ophthalmology, Lauderdale, April cannula simultaneously irrigatesFort both sides ofFlorida, the LASIK cannula simultaneously irrigates both sides of the LASIK 1997. flap, washes out the stromal bed, and enables flap reposiReprint requests out to Oliver D. Schein,bed, MD,and 116 enables Wilmer Bldg, flap, washes the stromal flapJohns repositioning. Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9019; fax: tioning. (410) 614-9651.
VOL.124, N O . 6
these anatomic features were asymptomatic; 10.5% (260/2,480) reported that they currently use artifi cial tears or lubricants. • CONCLUSIONS: Symptoms and signs of dry eye are common among the elderly but were not associated with age, race, or sex in this populationbased sample of elderly Americans. Extrapolating to the United States population aged 65 to 84 years, the study yields an estimate of 4.3 million who experience symptoms of ocular irritation often or all the time.
B
ASIC DESCRIPTIVE EPIDEMIOLOGIC DATA AVAIL-
able on dry eye have been unavailable in the United States. The classic teaching1 is that dry eye is largely a condition of menopausal and postmenis based opausal women. However, this presumption Visitec Company also announces the extension of the Visitec Company also announces the extension of the range of its portable Visitrec Vitrectomy System with clinic-based seriesVitrectomy of patients. Thewith pur-the entirely range on of its portable Visitrec System the
addition of the 5215 Visitrec Vitreous Biopsy Probe 00addition of the 5215 Visitrec Vitreous Biopsy Probe 00sephberg). The new probe provides one-step paracentesis, sephberg). The new probe provides one-step paracentesis, cutting, and See aspiration a single instrument. The 20-g 729-735, 736-750, also pp. with cutting, and aspiration with a single instrument. The 20-g guillotine cutting probe tapers to 23 gat 13.5 mm from the guillotine cutting probe tapers to 23 13.5 mm from the 751-757, 758-764, 765-774, andgat 825-835. tip, providing a guide to determine how far the probe has tip, providing a guide to determine how far the probe has been inserted. The MVR tip is .75 mm, and the aspiration been inserted. The MVR tip is .75 mm, and the aspiration portof is .5 mm,article The aspiration port is aligned with theand blade is to report prevalence pose port isthis .5 mm, The aspiration portthe is aligned with the blade edge for atraumatic insertion. The aspiration tube of the demographic features insertion. of dry eye based on a popula edge for atraumatic The aspiration tube of the hub indicates the orientation of both the aspiration port hub indicates theoforientation of both the aspiration port elderly Americans. tion-based sample and the blade edge. No suturing is required because the and theisblade edge. No that suturing requiredcondition because the a consensus the isclinical There MVR tip makes a small sclerotomy. The cutter automati2 MVR tip makes a small sclerotomy. The cutter automatidry ineye heterogeneous etiology.removal A termed cally stops theisopen position for in atraumatic cally stops in the open position for atraumatic removal recently National Eye Institute/Industry through convened the sclerotomy. through the sclerotomy. 2 Visitec Company also Trials presentsin two newEyes entries to itsto line Clinical Dry tried Workshop Visitecon Company also presents two new entries to its line of EdgeAhead Ophthalmic Surgical Knives series. The impose some orderOphthalmic and classification this heteroge of EdgeAhead SurgicaltoKnives series. The 1140and EdgeAhead IOLthat Knifethere 3.5 mm straight and 1141 recognized may be substantial neity 1140 EdgeAhead IOL Knife 3.5 mm straight and 1141 EdgeAhead IOL Knife 3.5 mm angled satisfy the surgeon's EdgeAhead IOL Knife 3.5 mmand angled satisfy the surgeon's in both symptoms clinical signs of overlap needs for a smaller IOL incision. All EdgeAhead Knives needs for a and smaller IOL incision. All Unfortunately, EdgeAhead Knives tear-deficient evaporative dry eye. feature a precise, sharp cutting edge for a clean incision and feature precise, sharp cutting edge forconfirm a clean incision and gold standard or rule there are ano reduced tissue distortion andtests havethat a nonglare matte finish reduced tissue distortion and have a nonglare matte finish the diagnosis. From clinical perspective, the out to minimize reflection froma microscope light. to minimize reflection from microscope light.
diagnosis is typically made based on the presence of
© AMERICAN JOURNAL OF OPHTHALMOLOGY 1997;124:723-728
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compatible symptoms and on varying support from the clinical examination and the results of readily available tests. The two tests historically most avail able to practitioners are the measurement of tear production with filter strips (Schirmer test) and the evaluation of ocular surface staining with the vital dye rose bengal. We recently demonstrated, using a popu lation-based sample, that there is relatively little overlap between individuals who have ocular surface symptoms, those who have low Schirmer test scores (defined as ^ 5 mm of wetting), and those who have high rose bengal staining (a score of ^5). 3 This lack of association and the underlying heterogeneity of the condition pose substantial challenges to presenting a unified definition of dry eye that incorporates both symptoms and test results. It is appropriate to diagnose and enumerate certain conditions based on the presence of laboratory evalu ation or other assessments, even in the absence of symptoms. For example, myocardial ischemia or infarct may be discoverable with electrocardiography while causing no symptoms yet pose a risk of sudden death. In the ophthalmic arena, glaucoma is asymp tomatic until an advanced stage, yet it is obviously important to diagnose this condition at an early, presymptomatic stage. Dry eye, however, rarely pro gresses to cause permanent damage in the absence of symptoms. Moreover, many clinicians would argue that the condition exists only when symptoms are present. In other words, abnormal results of a test or combination of tests in the absence of symptoms carry uncertain clinical significance and certainly would not warrant therapeutic intervention. There fore, all of the definitions of dry eye presented contain, as a sine qua non, the presence of symptoms.
SUBJECTS AND METHODS THE METHODS FOR THE RESEARCH PROJECT ON VISUAL
function and the elderly have been previously de scribed.4 To summarize briefly, the project goal was to recruit a random sample of residents of Salisbury, Maryland, aged 65 to 84 years, for participation in several distinct studies related to visual function and aging. Salisbury, located on Maryland's eastern shore, has a total population of 41,430, of whom 7,004 were aged 65 to 84 years in 1993.5 The sample was selected from the Health Care Financing Administration 724
Medicare database using the eligibility criteria of age between 65 and 84 years as of July 1, 1993, and a home zip code in the Salisbury metropolitan area. The older white population (75 to 84 years) was oversampled because of a presumed lower response rate, and a complete sample of black Americans was taken to ensure an adequate sample for comparison of rates with the white population. The initial contact with potential participants was by letter. Within 2 months of the letter, a trained interviewer contacted the individual, obtained in formed consent, and administered a standardized questionnaire in the home. Eligibility for an appoint ment at the examination facility also required the following: an ability to communicate verbally, an ability to travel to the facility (transportation was provided when requested), and a Mini-Mental State Examination6 score of 17 or higher. After each subject's initial recruitment into the study, an appointment at the examination facility was made. Once the subject's informed consent for partic ipation was obtained, a series of vision and functional status tests was performed, including the following dry eye evaluation. A six-item questionnaire pertain ing to dry eye symptoms3 was administered by a trained technician. For each symptom acknowledged, the respondent indicated whether he or she experi enced it rarely, sometimes, often, or all the time. Rose bengal assessment was performed using a micropipette to deliver 1 JULI of a 1% solution of preservativefree rose bengal after the instillation of one drop of a topical anesthetic, proparacaine hydrochloride. The scoring method of van Bijsterveld7 was used by a trained observer. Schirmer testing was performed a minimum of 30 minutes after rose bengal assessment. One drop of topical anesthetic was placed into each inferior conjunctival sac, followed by gentle blotting of visible fluid with tissue paper. A precalibrated filter strip was then placed temporally in each lower conjunctival fornix and left in place for 5 minutes, as timed on a stopwatch. After 5 minutes, the strips were removed, and the amount of wetting in millimeters was recorded from the precalibrated strips. After the dry eye evaluation, a trained examiner, who was masked to the results of the Schirmer and rose bengal tests and the questionnaire, assessed each subject's eyelid margin. The examiner visually graded the presence of collarettes and meibomian gland plugging
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER 1997
TABLE 1. Prevalence of Symptoms and Signs of Dry Eye No. (%) of Subjects Reporting a1 Symptom Often or All the Time and Abnormal
No. (%)
Test Result
of Subjects Reporting
Study Factor
Age group (yrs) 65-69 70-74 75-79 80+ Sex M F Race White Black Medical comorbidity 0-1 2-3 >4 Total
Schirmer Score
£1 Symptom
Schirmer
Rose Bengal
s 5 mm or
Schirmer Score £ 5 mm and
Often or All the Time*
Score s 5 mm
Score »5
Rose Bengal Score a 5
Rose Bengal Score a 5
774(14.2) 824(14.9) 540 (13.7) 344(16.3)
764 812 534 338
(2.5) (2.2) (1.3) (2.7)
757(1.6) 809 (2.4) 530 (1.7) 336 (2.4)
755 806 529 335
(3.2) (4.0) (2.5) (4.5)
1,052(13.3) 1,430(15.6)
1,048(1.5) 1,400 (2.6)
1,042(1.9) 1,390 (2.0)
1,042(2.6) 1,383(4.0)
1,041(0.7) 1,379 (0.7)
1,832(15.0) 650 (13.5)
1,809(2.4) 639(1.6)
1,804(2.2) 628(1.4)
1,797 (3.8) 628 (2.4)
1,794 (0.7) 626 (0.6)
778 (10.9) 1,168(13.1) 536 (23.3) 2,482 (14.6)
768 (2.5) 1,152(1.8) 528 (2.5) 2,448 (2.2)
767(1.7) 1,135(2.0) 530 (2.3) 2,432 (2.0)
763 (3.2) 1,135(3.4) 527 (4.0) 2,425 (3.5)
762(1.1) 1,131 (0.4) 527 (0.8) 2,420 (0.7)
754 804 528 334
(0.9) (0.6) (0.6) (0.6)
'Trend: xfn = 35.3; P < .001.
from 0 to 3 using a slit-lamp biomicroscope. A medical comorbidity score of from 0 to 15 was constructed for each participant based on the number of self-reported histories of the following 15 condi tions: arthritis, hip fracture, back problems, myocardial infarction, angina, congestive heart failure, intermittent claudication, hypertension, diabetes, em physema, asthma since age 50 years, stroke, Parkinson disease, cancer in the past 5 years, and vertigo. Prevalence estimates and 95% confidence intervals (CIs) are reported below. Comparisons of prevalence were performed using the Pearson chi-square statistic. Tests for trend in the association between number of comorbidities and prevalence of dry eye were performed using the Mantel-Haenzsel chi-square statistic.
RESULTS BETWEEN SEPTEMBER 1,1993, AND SEPTEMBER 15,1995, WE
recruited 2,520 subjects. The response rate for the clinic examination was 65% (2,520/3,906); 2,420 (96%) (2,420/2,520) of the subjects recruited com VOL.124, No. 6
pleted the dry eye evaluation. Table 1 presents the prevalence of dry eye by different definitions and by age group, sex, and race. Overall, 14.6% (363/2,482) of the members of the population (95% CI, 13.2% to 16.0%) reported experiencing one or more of the six symptoms of dry eye often or all the time. No statistically significant effect of age, sex, or race on this estimate was seen. A total of 18.1% of subjects (450/2,482) reported three or more symptoms to be present sometimes or more frequently. There was a prevalence of 2.2% (53/2,448) (95% CI, 1.6% to 2.8%) for individuals with one or more symptoms reported often or all the time and with a low Schirmer score (^5 mm) (Table 1). A cutoff of 5 mm was chosen because this threshold represent ed approximately the lower 10% tail of the entire pop ulation distribution (11.9% [290/2,448] had a low Schirmer test score) and because it is a value that has been used clinically by previous investigators. A total of 11.3% (275/2,432) of the population had a high rose bengal score (^5), for a prevalence of 2.0% (48/2,432) (95% CI, 1.4% to 2.6%) of the population who were symptomatic and had a high rose bengal score. There was a prevalence of 3.5%
PREVALENCE OF DRY EYE
725
TABLE 2. Associations With Dry Eye Symptoms
Characteristic
No. (%) of Subjects Reporting a 1 Symptom*
P Value'
Blepharitis (physical signs) Present 88 (23.9) Absent 2,381 (14.2) Prior diagnosis of dry eye/blepharitis Yes 85 (42.4) No 2,389(13.6) Visit to an eye care professional in past year Yes 1,591 (16.7) No 885(11.0) Current use of artificial tears Yes 260 (34.2) No 2,220(12.3) Schirmer test score (mm) £5 290(18.3) >5 2,158(14.2) Rose bengal test score a5 275 (17.5) <5 2,157(14.3)
.01
<.0001
<.001
<.001
.06
.167
'Reported that dry eye symptom is present often or all the time. tChi-square test for proportions.
(84/2,425) (95% CI, 2.8% to 4.2%) for individuals who reported symptoms often or all the time and who had either a low Schirmer or a high rose bengal score. Finally, there was a prevalence of 0.7% (17/2,420) (95% CI, 0.41% to 1.12%) of the population who were symptomatic and had both a low Schirmer and a high rose bengal score (Table 1). For none of the definitions was there a significant effect of age, race, or sex on the prevalence of dry eye. The estimated prevalence and the lack of association was not affected by adjusting for nonresponse. Individuals reporting their general health to be poor were significantly (P < .001) more likely (16.9% [269/1,571] vs 10.6% [94/886]) to report dry eye symptoms to be present often or all the time than were individuals reporting their overall health to be good. However, no association was seen between either Schirmer or rose bengal test scores and selfreported general health. The presence of more medi cal comorbidity was also strongly associated (P < .001) with reported symptoms of dry eye. Again, no association was seen between medical comorbidity 726
and Schirmer or rose bengal test scores. Table 2 shows the association between symptoms of dry eye and other related conditions and use of ophthalmic care products. Eighty-eight individuals had anatomic features of meibomianitis, as reflected by a slit-lamp grade of 2 or 3 for collarettes or meibomian gland plugging. Although only 21 (24%) of these individuals were symptomatic, they were almost twice as likely (P = .01) to have dry eye symptoms as were those without these anatomic features. Eighty-five participants (3.4% of the total population of 2,482 subjects) indicated that they had previously been given a diagnosis of dry eye. Of this group, 42% (36/85) were symptomatic. Overall, 64% (1,591/2,482) of the population indicated that they had visited an eye care professional during the past year, and this group was approximately 60% more likely to report symptoms. Of those indicating symptoms often or all the time, 73% (265/363) reported seeing an eye care profes sional during the previous year. Only 10% (36/363) of these reported receiving any clinical diagnosis relating to their symptoms; 25% (89/363) of symptom atic individuals reported current use of artificial tears or lubricants. The current use of artificial tears and ocular lubricants was reported by 10.5% (260/2,480) of the entire population. Subjects who used these supplements were approximately three times more likely than those not using supplements to report the presence of symptoms often or all the time. However, they were neither more nor less likely to exhibit rose bengal staining or low Schirmer test scores.
DISCUSSION SYMPTOMS OF OCULAR IRRITATION COMPATIBLE WITH
dry eye were found to be common in our populationbased sample of elderly Americans, with 14.6% (363/2,482) reporting one or more symptoms to be present often or all the time. An extrapolation from our population to the US population aged 65 years or older yields an estimate of 4.3 million Americans between the ages of 65 and 84 years who suffer from symptoms of ocular irritation often or all the time. It is impossible to know whether the estimates generated in Salisbury, Maryland, can be accurately projected nationally. However, this possibility is enhanced by a lack of sex, race, and age effects in our sample and the
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER
1997
fact that the sample was population based. Recently, a National Eye Institute/Industry Work shop on Clinical Trials in Dry Eyes2 recognized the heterogeneity of dry eye and proposed a classification scheme based on tear-deficient dry eye (for example, low tear volume) and evaporative dry eye (for exam ple, blepharitis, mucin deficiencies, and blink disor ders). A global definition of dry eye was proposed, which described it as "a disorder of the tear film due to tear deficiency or excessive tear evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discom fort."2 However, the workshop also recognized that signs may be present in the absence of symptoms and that a dry eye state may exist as supported by both symptoms and signs (for example, reduced tear secre tion), yet current techniques may be unable to document ocular surface damage. Clearly, the estimated prevalence of dry eye will vary substantially by the definitions and thresholds selected. Because asymptomatic dry eye (dry eye based on measurement of tear production alone) is of uncertain clinical importance, symptoms reported to be present often or all the time form the minimum basis in this report for diagnosis of dry eye. Schirmer and rose bengal testing were chosen as the principal tests because of their common historical clinical use and their adaptability to afieldepidemiologic setting. A prevalence of 3.5% was estimated for the combina tion of dry eye symptoms and the presence of a low Schirmer test score or high rose bengal score. Because these two tests measure different aspects of physiolog ic function, each of which is believed to be related to a dry eye state, there is a logical appeal to invoking this definition of dry eye. Again, extrapolating to the entire US population, this estimate indicates that approximately 1 million Americans between the ages of 65 and 84 years would meet this definition. No difference in the prevalence of dry eye was seen by race, sex, or age group. This finding is of interest because one would infer on the basis of clinic-based observation that dry eye principally affects elderly white women. As we have previously speculated,3 this may be because of various referral and selection biases in clinic-based series and because the study popula tion included only the elderly, without younger groups for comparison. The association of both self-reported poor health VOL.124, No. 6
and medical comorbidity with dry eye symptoms and their lack of association with Schirmer and rose bengal test results are of interest. It is possible that this represents a true association of dry eye with other illnesses or perhaps with the medicines used to treat the medical conditions. Conversely, this finding could reflect reporting bias, wherein subjects report ing poor health or illness are simply more likely to report symptoms in general. Research efforts on this population, which will include medical record ab straction and analysis of prescription drug use, may help to clarify these observed associations. Of the subjects indicating the presence of symp toms often or all the time, 64% (1,591/2,482) had seen an eye care professional within the previous year. Only 10% (36/363) had been given a diagnosis compatible with their symptoms, and 25% (89/363) were using artificial tears or lubricants. These findings suggest that there is a substantial unmet need regard ing the diagnosis and attempted treatment of com mon ocular surface disorders. The design of the present study, however, does not permit inference regarding the potential effectiveness of such treatment in reducing symptoms. Current use of over-thecounter ocular lubricants by this population is 10.5% (260/2,480). Again, extrapolating to the US popula tion would indicate that approximately 3 million elderly Americans currently use nonprescription ocu lar lubricants. If this is true, then the current poten tial market for such agents is enormous, particularly if their clinical efficacy can be demonstrated. In summary, this population-based cohort had a dry eye prevalence of 14.6% when this condition was defined on the basis of symptoms alone and a prevalence of 3.5% based on the presence of symp toms and one or more signs. No association with race, sex, or age was established. Further research will attempt to define risk factors for dry eye and study potential associations with dry mouth, systemic dis ease, and serologic evidence of autoimmunity.
REFERENCES 1. Lemp MA. Diagnosis and treatment of tear deficiencies. In: Tasman W, Jaeger EA, editors. Duane's clinical ophthalmolo gy. Volume 4. Chapter 14. Philadelphia: Lippincott-Raven, 1995:109. 2. Lemp MA. Report of the National Eye Institute/Industry
PREVALENCE OF DRY EYE
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Workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21: 221-232. 3. Schein OD, Tielsch JM, Mufioz B, Bandeen-Roche K, West S. Relationship between signs and symptoms of dry eye: a population-based perspective. Ophthalmology 1997;104: 1395-1401. 4. West S, Mufioz B, Rubin G, et al, and the SEE Project Team. Function and visual impairment in a population-based study of older adults: SEE Project. Invest Ophthalmol Vis Sci 1997;38:72-82.
5. Maryland Office of Planning, Division of Business Develop ment. Population projections. June 1990. 6. Folstein MF, Folstein SE, McHugh PR. 'Mini-mental state': a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198. 7. van Bijsterveld OP. Diagnostic tests in the sicca syndrome. Arch Ophthalmol 1969;82:10-14.
Authors Interactive™ Comments and questions regarding this article may be addressed to authors via THE JOURNAL'S Web Site. Selected comments, questions, and author responses are posted on Authors Interactive™ at http://www.ajo.com/
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PRODUCTS PRODUCTS AND AND SERVICES SERVICES • PURPOSE: To study the demographics and esti mate the prevalence of dry eye among elderly Americans. PRODUCTS AND population-based SERVICES CONSIDEREDprevalence TO BE OF IN. • NEW METHODS: NEW PRODUCTSAAND SERVICES CONSIDERED TO BE OF IN. terest to our readers are described on the of 2,520 residents of basis Salis study wasto performed terest our readersinare described on the basis of information supplied by the companies cited. Publication years andcited. older as of bury, Maryland, agedby 65 information supplied the companies Publication of these notices does not imply endorsement or warranty of these notices doesThe not imply endorsement warranty September 1993. population was or derived by The Ophthalmic Publishing Company, publishers of by The Publishing Company, publishers of the Ophthalmic Health Care Financing Administration from the AMERICAN JOURNAL OF OPHTHALMOLOGY, for these the AMERICAN JOURNAL OF OPHTHALMOLOGY, for these Medicare database. After completing a standard products and services. products and services. ized questionnaire pertaining to dry eye symp toms, 2,420 subjects underwent Schirmer and rose bengal tests and anatomic assessment of the meibomian glands. • RESULTS: In this population, 14.6% (363/ 2,482) were symptomatic, denned as reporting one or more drySURGICAL eye symptoms often or all the time; SURGICAL INSTRUMENTS INSTRUMENTS 2.2% (53/2,448) were symptomatic and had a low Schirmer test result (^5 mm), and 2% (48/2,432) were symptomatic and had a high rose bengal test score (^5). Furthermore, 3.5% (84/2,425) were symptomatic and had either a low Schirmer score or a high rose bengal score, and 0.7% (17/2,420) were symptomatic and had both a low Schirmer score and a high rose bengal score. No association of symptoms or signs was seen with age, sex, or race. Although anatomic features of meibomianitis were associated with the presence of symptoms (P = .01), 76% (67/88) of the individuals with
• Visitec Company, 7575 Commerce Court, Sarasota, • Visitec Company, 7575 Commerce Court, Sarasota, FLA 34243; telephone: (800) 237-2174 or (940 FLA for34243; telephone: or (940 Accepted publication May 7,705-2525 1997. (800) 237-2174 359-9883; fax: (800) Company intro359-9883; fax: (800) 705-2525Visitec Visitec Company introFrom the Department of Ophthalmology (Drs Schein, Tielsch, and duces 5216 Department LASIK Flap Irrigator Health (Vidaurri), which West, and the Ms Muftoz), of International (Dr Tielsch), duces the 5216 LASIK Flap Irrigator (Vidaurri), which and Department Biostatistics Bandeen-Roche), The Johns Hop45 features two of parallel .50 x(Dr 13-mm tip extensions angled two parallelMaryland. .50 x 13-mm tipbyextensions angled 45 kinsfeatures University, Baltimore, Supported grant PO1AG10184 degrees and placed 1 mm apart. Each extension possesses fromdegrees the National Bethesda, Maryland. Data from this andInstitute placedof1Aging, mm apart. Each extension possesses fourwere ports, twoin inside twomeeting outside. universal study presented at theand annual of the The Association for four ports, two part inside and two outside. The universal Research in Vision and Ophthalmology, Lauderdale, April cannula simultaneously irrigatesFort both sides ofFlorida, the LASIK cannula simultaneously irrigates both sides of the LASIK 1997. flap, washes out the stromal bed, and enables flap reposiReprint requests out to Oliver D. Schein,bed, MD,and 116 enables Wilmer Bldg, flap, washes the stromal flapJohns repositioning. Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9019; fax: tioning. (410) 614-9651.
VOL.124, N O . 6
these anatomic features were asymptomatic; 10.5% (260/2,480) reported that they currently use artifi cial tears or lubricants. • CONCLUSIONS: Symptoms and signs of dry eye are common among the elderly but were not associated with age, race, or sex in this populationbased sample of elderly Americans. Extrapolating to the United States population aged 65 to 84 years, the study yields an estimate of 4.3 million who experience symptoms of ocular irritation often or all the time.
B
ASIC DESCRIPTIVE EPIDEMIOLOGIC DATA AVAIL-
able on dry eye have been unavailable in the United States. The classic teaching1 is that dry eye is largely a condition of menopausal and postmenis based opausal women. However, this presumption Visitec Company also announces the extension of the Visitec Company also announces the extension of the range of its portable Visitrec Vitrectomy System with clinic-based seriesVitrectomy of patients. Thewith pur-the entirely range on of its portable Visitrec System the
addition of the 5215 Visitrec Vitreous Biopsy Probe 00addition of the 5215 Visitrec Vitreous Biopsy Probe 00sephberg). The new probe provides one-step paracentesis, sephberg). The new probe provides one-step paracentesis, cutting, and See aspiration a single instrument. The 20-g 729-735, 736-750, also pp. with cutting, and aspiration with a single instrument. The 20-g guillotine cutting probe tapers to 23 gat 13.5 mm from the guillotine cutting probe tapers to 23 13.5 mm from the 751-757, 758-764, 765-774, andgat 825-835. tip, providing a guide to determine how far the probe has tip, providing a guide to determine how far the probe has been inserted. The MVR tip is .75 mm, and the aspiration been inserted. The MVR tip is .75 mm, and the aspiration portof is .5 mm,article The aspiration port is aligned with theand blade is to report prevalence pose port isthis .5 mm, The aspiration portthe is aligned with the blade edge for atraumatic insertion. The aspiration tube of the demographic features insertion. of dry eye based on a popula edge for atraumatic The aspiration tube of the hub indicates the orientation of both the aspiration port hub indicates theoforientation of both the aspiration port elderly Americans. tion-based sample and the blade edge. No suturing is required because the and theisblade edge. No that suturing requiredcondition because the a consensus the isclinical There MVR tip makes a small sclerotomy. The cutter automati2 MVR tip makes a small sclerotomy. The cutter automatidry ineye heterogeneous etiology.removal A termed cally stops theisopen position for in atraumatic cally stops in the open position for atraumatic removal recently National Eye Institute/Industry through convened the sclerotomy. through the sclerotomy. 2 Visitec Company also Trials presentsin two newEyes entries to itsto line Clinical Dry tried Workshop Visitecon Company also presents two new entries to its line of EdgeAhead Ophthalmic Surgical Knives series. The impose some orderOphthalmic and classification this heteroge of EdgeAhead SurgicaltoKnives series. The 1140and EdgeAhead IOLthat Knifethere 3.5 mm straight and 1141 recognized may be substantial neity 1140 EdgeAhead IOL Knife 3.5 mm straight and 1141 EdgeAhead IOL Knife 3.5 mm angled satisfy the surgeon's EdgeAhead IOL Knife 3.5 mmand angled satisfy the surgeon's in both symptoms clinical signs of overlap needs for a smaller IOL incision. All EdgeAhead Knives needs for a and smaller IOL incision. All Unfortunately, EdgeAhead Knives tear-deficient evaporative dry eye. feature a precise, sharp cutting edge for a clean incision and feature precise, sharp cutting edge forconfirm a clean incision and gold standard or rule there are ano reduced tissue distortion andtests havethat a nonglare matte finish reduced tissue distortion and have a nonglare matte finish the diagnosis. From clinical perspective, the out to minimize reflection froma microscope light. to minimize reflection from microscope light.
diagnosis is typically made based on the presence of
© AMERICAN JOURNAL OF OPHTHALMOLOGY 1997;124:723-728
723
compatible symptoms and on varying support from the clinical examination and the results of readily available tests. The two tests historically most avail able to practitioners are the measurement of tear production with filter strips (Schirmer test) and the evaluation of ocular surface staining with the vital dye rose bengal. We recently demonstrated, using a popu lation-based sample, that there is relatively little overlap between individuals who have ocular surface symptoms, those who have low Schirmer test scores (defined as ^ 5 mm of wetting), and those who have high rose bengal staining (a score of ^5). 3 This lack of association and the underlying heterogeneity of the condition pose substantial challenges to presenting a unified definition of dry eye that incorporates both symptoms and test results. It is appropriate to diagnose and enumerate certain conditions based on the presence of laboratory evalu ation or other assessments, even in the absence of symptoms. For example, myocardial ischemia or infarct may be discoverable with electrocardiography while causing no symptoms yet pose a risk of sudden death. In the ophthalmic arena, glaucoma is asymp tomatic until an advanced stage, yet it is obviously important to diagnose this condition at an early, presymptomatic stage. Dry eye, however, rarely pro gresses to cause permanent damage in the absence of symptoms. Moreover, many clinicians would argue that the condition exists only when symptoms are present. In other words, abnormal results of a test or combination of tests in the absence of symptoms carry uncertain clinical significance and certainly would not warrant therapeutic intervention. There fore, all of the definitions of dry eye presented contain, as a sine qua non, the presence of symptoms.
SUBJECTS AND METHODS THE METHODS FOR THE RESEARCH PROJECT ON VISUAL
function and the elderly have been previously de scribed.4 To summarize briefly, the project goal was to recruit a random sample of residents of Salisbury, Maryland, aged 65 to 84 years, for participation in several distinct studies related to visual function and aging. Salisbury, located on Maryland's eastern shore, has a total population of 41,430, of whom 7,004 were aged 65 to 84 years in 1993.5 The sample was selected from the Health Care Financing Administration 724
Medicare database using the eligibility criteria of age between 65 and 84 years as of July 1, 1993, and a home zip code in the Salisbury metropolitan area. The older white population (75 to 84 years) was oversampled because of a presumed lower response rate, and a complete sample of black Americans was taken to ensure an adequate sample for comparison of rates with the white population. The initial contact with potential participants was by letter. Within 2 months of the letter, a trained interviewer contacted the individual, obtained in formed consent, and administered a standardized questionnaire in the home. Eligibility for an appoint ment at the examination facility also required the following: an ability to communicate verbally, an ability to travel to the facility (transportation was provided when requested), and a Mini-Mental State Examination6 score of 17 or higher. After each subject's initial recruitment into the study, an appointment at the examination facility was made. Once the subject's informed consent for partic ipation was obtained, a series of vision and functional status tests was performed, including the following dry eye evaluation. A six-item questionnaire pertain ing to dry eye symptoms3 was administered by a trained technician. For each symptom acknowledged, the respondent indicated whether he or she experi enced it rarely, sometimes, often, or all the time. Rose bengal assessment was performed using a micropipette to deliver 1 JULI of a 1% solution of preservativefree rose bengal after the instillation of one drop of a topical anesthetic, proparacaine hydrochloride. The scoring method of van Bijsterveld7 was used by a trained observer. Schirmer testing was performed a minimum of 30 minutes after rose bengal assessment. One drop of topical anesthetic was placed into each inferior conjunctival sac, followed by gentle blotting of visible fluid with tissue paper. A precalibrated filter strip was then placed temporally in each lower conjunctival fornix and left in place for 5 minutes, as timed on a stopwatch. After 5 minutes, the strips were removed, and the amount of wetting in millimeters was recorded from the precalibrated strips. After the dry eye evaluation, a trained examiner, who was masked to the results of the Schirmer and rose bengal tests and the questionnaire, assessed each subject's eyelid margin. The examiner visually graded the presence of collarettes and meibomian gland plugging
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER 1997
TABLE 1. Prevalence of Symptoms and Signs of Dry Eye No. (%) of Subjects Reporting a1 Symptom Often or All the Time and Abnormal
No. (%)
Test Result
of Subjects Reporting
Study Factor
Age group (yrs) 65-69 70-74 75-79 80+ Sex M F Race White Black Medical comorbidity 0-1 2-3 >4 Total
Schirmer Score
£1 Symptom
Schirmer
Rose Bengal
s 5 mm or
Schirmer Score £ 5 mm and
Often or All the Time*
Score s 5 mm
Score »5
Rose Bengal Score a 5
Rose Bengal Score a 5
774(14.2) 824(14.9) 540 (13.7) 344(16.3)
764 812 534 338
(2.5) (2.2) (1.3) (2.7)
757(1.6) 809 (2.4) 530 (1.7) 336 (2.4)
755 806 529 335
(3.2) (4.0) (2.5) (4.5)
1,052(13.3) 1,430(15.6)
1,048(1.5) 1,400 (2.6)
1,042(1.9) 1,390 (2.0)
1,042(2.6) 1,383(4.0)
1,041(0.7) 1,379 (0.7)
1,832(15.0) 650 (13.5)
1,809(2.4) 639(1.6)
1,804(2.2) 628(1.4)
1,797 (3.8) 628 (2.4)
1,794 (0.7) 626 (0.6)
778 (10.9) 1,168(13.1) 536 (23.3) 2,482 (14.6)
768 (2.5) 1,152(1.8) 528 (2.5) 2,448 (2.2)
767(1.7) 1,135(2.0) 530 (2.3) 2,432 (2.0)
763 (3.2) 1,135(3.4) 527 (4.0) 2,425 (3.5)
762(1.1) 1,131 (0.4) 527 (0.8) 2,420 (0.7)
754 804 528 334
(0.9) (0.6) (0.6) (0.6)
'Trend: xfn = 35.3; P < .001.
from 0 to 3 using a slit-lamp biomicroscope. A medical comorbidity score of from 0 to 15 was constructed for each participant based on the number of self-reported histories of the following 15 condi tions: arthritis, hip fracture, back problems, myocardial infarction, angina, congestive heart failure, intermittent claudication, hypertension, diabetes, em physema, asthma since age 50 years, stroke, Parkinson disease, cancer in the past 5 years, and vertigo. Prevalence estimates and 95% confidence intervals (CIs) are reported below. Comparisons of prevalence were performed using the Pearson chi-square statistic. Tests for trend in the association between number of comorbidities and prevalence of dry eye were performed using the Mantel-Haenzsel chi-square statistic.
RESULTS BETWEEN SEPTEMBER 1,1993, AND SEPTEMBER 15,1995, WE
recruited 2,520 subjects. The response rate for the clinic examination was 65% (2,520/3,906); 2,420 (96%) (2,420/2,520) of the subjects recruited com VOL.124, No. 6
pleted the dry eye evaluation. Table 1 presents the prevalence of dry eye by different definitions and by age group, sex, and race. Overall, 14.6% (363/2,482) of the members of the population (95% CI, 13.2% to 16.0%) reported experiencing one or more of the six symptoms of dry eye often or all the time. No statistically significant effect of age, sex, or race on this estimate was seen. A total of 18.1% of subjects (450/2,482) reported three or more symptoms to be present sometimes or more frequently. There was a prevalence of 2.2% (53/2,448) (95% CI, 1.6% to 2.8%) for individuals with one or more symptoms reported often or all the time and with a low Schirmer score (^5 mm) (Table 1). A cutoff of 5 mm was chosen because this threshold represent ed approximately the lower 10% tail of the entire pop ulation distribution (11.9% [290/2,448] had a low Schirmer test score) and because it is a value that has been used clinically by previous investigators. A total of 11.3% (275/2,432) of the population had a high rose bengal score (^5), for a prevalence of 2.0% (48/2,432) (95% CI, 1.4% to 2.6%) of the population who were symptomatic and had a high rose bengal score. There was a prevalence of 3.5%
PREVALENCE OF DRY EYE
725
TABLE 2. Associations With Dry Eye Symptoms
Characteristic
No. (%) of Subjects Reporting a 1 Symptom*
P Value'
Blepharitis (physical signs) Present 88 (23.9) Absent 2,381 (14.2) Prior diagnosis of dry eye/blepharitis Yes 85 (42.4) No 2,389(13.6) Visit to an eye care professional in past year Yes 1,591 (16.7) No 885(11.0) Current use of artificial tears Yes 260 (34.2) No 2,220(12.3) Schirmer test score (mm) £5 290(18.3) >5 2,158(14.2) Rose bengal test score a5 275 (17.5) <5 2,157(14.3)
.01
<.0001
<.001
<.001
.06
.167
'Reported that dry eye symptom is present often or all the time. tChi-square test for proportions.
(84/2,425) (95% CI, 2.8% to 4.2%) for individuals who reported symptoms often or all the time and who had either a low Schirmer or a high rose bengal score. Finally, there was a prevalence of 0.7% (17/2,420) (95% CI, 0.41% to 1.12%) of the population who were symptomatic and had both a low Schirmer and a high rose bengal score (Table 1). For none of the definitions was there a significant effect of age, race, or sex on the prevalence of dry eye. The estimated prevalence and the lack of association was not affected by adjusting for nonresponse. Individuals reporting their general health to be poor were significantly (P < .001) more likely (16.9% [269/1,571] vs 10.6% [94/886]) to report dry eye symptoms to be present often or all the time than were individuals reporting their overall health to be good. However, no association was seen between either Schirmer or rose bengal test scores and selfreported general health. The presence of more medi cal comorbidity was also strongly associated (P < .001) with reported symptoms of dry eye. Again, no association was seen between medical comorbidity 726
and Schirmer or rose bengal test scores. Table 2 shows the association between symptoms of dry eye and other related conditions and use of ophthalmic care products. Eighty-eight individuals had anatomic features of meibomianitis, as reflected by a slit-lamp grade of 2 or 3 for collarettes or meibomian gland plugging. Although only 21 (24%) of these individuals were symptomatic, they were almost twice as likely (P = .01) to have dry eye symptoms as were those without these anatomic features. Eighty-five participants (3.4% of the total population of 2,482 subjects) indicated that they had previously been given a diagnosis of dry eye. Of this group, 42% (36/85) were symptomatic. Overall, 64% (1,591/2,482) of the population indicated that they had visited an eye care professional during the past year, and this group was approximately 60% more likely to report symptoms. Of those indicating symptoms often or all the time, 73% (265/363) reported seeing an eye care profes sional during the previous year. Only 10% (36/363) of these reported receiving any clinical diagnosis relating to their symptoms; 25% (89/363) of symptom atic individuals reported current use of artificial tears or lubricants. The current use of artificial tears and ocular lubricants was reported by 10.5% (260/2,480) of the entire population. Subjects who used these supplements were approximately three times more likely than those not using supplements to report the presence of symptoms often or all the time. However, they were neither more nor less likely to exhibit rose bengal staining or low Schirmer test scores.
DISCUSSION SYMPTOMS OF OCULAR IRRITATION COMPATIBLE WITH
dry eye were found to be common in our populationbased sample of elderly Americans, with 14.6% (363/2,482) reporting one or more symptoms to be present often or all the time. An extrapolation from our population to the US population aged 65 years or older yields an estimate of 4.3 million Americans between the ages of 65 and 84 years who suffer from symptoms of ocular irritation often or all the time. It is impossible to know whether the estimates generated in Salisbury, Maryland, can be accurately projected nationally. However, this possibility is enhanced by a lack of sex, race, and age effects in our sample and the
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER
1997
fact that the sample was population based. Recently, a National Eye Institute/Industry Work shop on Clinical Trials in Dry Eyes2 recognized the heterogeneity of dry eye and proposed a classification scheme based on tear-deficient dry eye (for example, low tear volume) and evaporative dry eye (for exam ple, blepharitis, mucin deficiencies, and blink disor ders). A global definition of dry eye was proposed, which described it as "a disorder of the tear film due to tear deficiency or excessive tear evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discom fort."2 However, the workshop also recognized that signs may be present in the absence of symptoms and that a dry eye state may exist as supported by both symptoms and signs (for example, reduced tear secre tion), yet current techniques may be unable to document ocular surface damage. Clearly, the estimated prevalence of dry eye will vary substantially by the definitions and thresholds selected. Because asymptomatic dry eye (dry eye based on measurement of tear production alone) is of uncertain clinical importance, symptoms reported to be present often or all the time form the minimum basis in this report for diagnosis of dry eye. Schirmer and rose bengal testing were chosen as the principal tests because of their common historical clinical use and their adaptability to afieldepidemiologic setting. A prevalence of 3.5% was estimated for the combina tion of dry eye symptoms and the presence of a low Schirmer test score or high rose bengal score. Because these two tests measure different aspects of physiolog ic function, each of which is believed to be related to a dry eye state, there is a logical appeal to invoking this definition of dry eye. Again, extrapolating to the entire US population, this estimate indicates that approximately 1 million Americans between the ages of 65 and 84 years would meet this definition. No difference in the prevalence of dry eye was seen by race, sex, or age group. This finding is of interest because one would infer on the basis of clinic-based observation that dry eye principally affects elderly white women. As we have previously speculated,3 this may be because of various referral and selection biases in clinic-based series and because the study popula tion included only the elderly, without younger groups for comparison. The association of both self-reported poor health VOL.124, No. 6
and medical comorbidity with dry eye symptoms and their lack of association with Schirmer and rose bengal test results are of interest. It is possible that this represents a true association of dry eye with other illnesses or perhaps with the medicines used to treat the medical conditions. Conversely, this finding could reflect reporting bias, wherein subjects report ing poor health or illness are simply more likely to report symptoms in general. Research efforts on this population, which will include medical record ab straction and analysis of prescription drug use, may help to clarify these observed associations. Of the subjects indicating the presence of symp toms often or all the time, 64% (1,591/2,482) had seen an eye care professional within the previous year. Only 10% (36/363) had been given a diagnosis compatible with their symptoms, and 25% (89/363) were using artificial tears or lubricants. These findings suggest that there is a substantial unmet need regard ing the diagnosis and attempted treatment of com mon ocular surface disorders. The design of the present study, however, does not permit inference regarding the potential effectiveness of such treatment in reducing symptoms. Current use of over-thecounter ocular lubricants by this population is 10.5% (260/2,480). Again, extrapolating to the US popula tion would indicate that approximately 3 million elderly Americans currently use nonprescription ocu lar lubricants. If this is true, then the current poten tial market for such agents is enormous, particularly if their clinical efficacy can be demonstrated. In summary, this population-based cohort had a dry eye prevalence of 14.6% when this condition was defined on the basis of symptoms alone and a prevalence of 3.5% based on the presence of symp toms and one or more signs. No association with race, sex, or age was established. Further research will attempt to define risk factors for dry eye and study potential associations with dry mouth, systemic dis ease, and serologic evidence of autoimmunity.
REFERENCES 1. Lemp MA. Diagnosis and treatment of tear deficiencies. In: Tasman W, Jaeger EA, editors. Duane's clinical ophthalmolo gy. Volume 4. Chapter 14. Philadelphia: Lippincott-Raven, 1995:109. 2. Lemp MA. Report of the National Eye Institute/Industry
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Workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21: 221-232. 3. Schein OD, Tielsch JM, Mufioz B, Bandeen-Roche K, West S. Relationship between signs and symptoms of dry eye: a population-based perspective. Ophthalmology 1997;104: 1395-1401. 4. West S, Mufioz B, Rubin G, et al, and the SEE Project Team. Function and visual impairment in a population-based study of older adults: SEE Project. Invest Ophthalmol Vis Sci 1997;38:72-82.
5. Maryland Office of Planning, Division of Business Develop ment. Population projections. June 1990. 6. Folstein MF, Folstein SE, McHugh PR. 'Mini-mental state': a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198. 7. van Bijsterveld OP. Diagnostic tests in the sicca syndrome. Arch Ophthalmol 1969;82:10-14.
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