A C T A 0 P H T H A L M 0 LOG I C A
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Tear film profile in Graves’ ophthalmopathy A. K. Khurana’, Sham Sunder’, B. K. Ahluwalia’ and K. C. Malhotra2 Departments of Ophthalmology’and Medicine‘, Medical College & Hospital, Rohtak, India
Abstract. Tear film profile was studied in 30 patients with Graves’ ophthalmopathy.Tear film pH, fluorescein staining, marginal tear strip and Schimer test values in patients with Graves’ ophthalmopathywere comparable with controls,indicating normal tear secretion. Tear film break-up-time (BUT) in late Graves’ ophthalmopathy was significantlylow suggesting unstable tear film. Rose bengal as well as lissamine green staining intensity scores were signiGcantly high, indicating presence of drying epithelial cells in early as well as late Graves’ ophthalmopathy patients. Key words: Graves’ ophthalmopathy - tear film - dry eye.
Patients with Graves’ ophthalmopathy frequently have symptoms of ocular surface discomfort strikingly similar as to those found in dry eye (Perlmutter et al. 1977; Werner 1971). The drying of ocular surface has been attributed to corneal exposure (Perlmutter et al. 1977; Werner 1971). Increased palpebral fissure width in patients with Graves’ ophthalmopathy may accelerate tear f ilm evaporation (Gilbard & Farris 1983). Tear film profile was studied in detail in the present work in order to comment on frequency, pattern and pathophysiology of ocular surface drying in Graves’ ophthalmopathy.
Material and Methods The present study was undertaken in 30 randomly selected cases of Graves’ophthalmopathy. Patients
346
with other associated conditions leading to abnormalities of tear film flow and/or stability and those using artificial tears were not included in the study. Each patient conformed to one of the classes of Graves’ ophthalmopathy as classified by American Thyroid Association (ATA) (Werner 1969), irrespective of the hormonal status. For the purpose of analysing the results, cases were divided into early (ATA-class 1 and 2) and late Graves’ ophthalmopathy (ATA-class 3 to 6). In each patient the width of palpebral fissure was measured as described by Fox (1966) and number of blinks per minute were counted using the sham of palpating the radial pulse. Exophthalmometry was carried out in erect position using Hertel’s exophthalmometer. Tear film profile was studied in detail as described elsewhere (JShurana et al. 1991). In addition, 30 age and sex matched controls also underwent similar investigations.The results were computed and analysed.
Results Out of 30 patients with Graves’ ophthalmopathy, 18 were females and 12 males with a female-male ratio of 1.5:l. The mean age was 32.73 k9.42 (range 17-50 years). The controls were age (mean 33.53 k 9.71, range 18-50) and sex (16 females and 14 males) matched. In accordance with thyroid status, 19 (63.33%)were hyperthyroid and 11 (36.67%)euthyroid. None of the patients had hypothyroidism.
Group
Control Early Graves’ ophthalmopathy Late Graves’ ophthalmopathy
No. of subjects
Exophthalmometry readings (in mm)
30 15 15
All the controls were euthyroid. Fifteen patients each were with early and late Graves’ ophthalmopathy. The mean palpebral fissure width noted in controls and patients with early and late Graves’ ophthalmopathy was 10.6 f 0.91, 12.4 f 1.50, and 14.53 f 1.55 mm, respectively.The mean blink rate was 14.26 f 3.31 in controls and 15.33 k 4.92 and 15.26 f8.94 in patients with early and late Graves’ ophthalmopathy,respectively.Exophthalmometry readings in patients with Graves’ ophthalmopathy and controls are shown in Table 1. The values of different tear function tests in patients with early
Right eye
Left eye
15.06 f 1.38 16.0 f 1.81 20.1 52.53
15.23 f 1.33 16.13 f 1.59 19.8 f 2 . 6 2
and late Graves’ ophthalmopathy and controls are depicted in Table 2. Distribution of patients, based on tear film profile, into different grades according to Khurana’s criteria (1991) is shown in Table 3.
Discussion Drying of ocular surface in Graves’ ophthalmopathy is thought to result from exposure attributed to upper lid retraction, exopathalmos, lagophthalmos,inability to elevate the eyes and a de-
Graves’ ophthalmopathy patients S. No.
Tear function tests
Early (n: 15)
Late (n: 15)
Controls (n: 30)
347
Table 3. Distribution of cases into different grades of d r y eye (Khurana et al. 1991).
Number of cases (per cent) Grade of dry eye
Total score
Graves’ ophthalmopathy patiens Controls Early
No dry eye Dry eye suspect Mild dry eye Moderate dry eye Severe dry eye
creased blink rate (Perlmutter et al. 1977; Werner 1971). An attempt has been made in the present study to comment on the tear film profile in patients with Graves’ophthalmopathy. Mean palpebral fissure width was significantly high in early as well as late Graves’ ophthalmopathy cases. Similar observations have been made by other workers (Gilbard& Farris 1983).It can be attributed to lid retraction and exophthalmos. Stellwag‘s sign, i.e. infrequent blinking, in Graves’ ophthalmopathy is in contrast to high blink rate noted in the present study. Gilbard and Farris (1983)also noted increased blink rate and consider it due to increased ocular surface irritation. A scanty,discontinousor absent tear meniscus is an important sign of dry eye (Whitcher 1987). None of the patients with Graves’ophthalmopathy had discontinuous or absent tear strip in the present study. The values of BUT observed in early Graves’ ophthalmopathy patients (12.21 f 2.09) were comparable with controls (12.42 f 2.55 sec), whereas in late Graves’ ophthalmopathy BUT (6.61 f 2.79) was significantly less ( P < 0.001) than the controls and reported cut off point of 10 seconds in an Indian population (Moudgilet al.1989). Gilbard & Farris (1983)also found decreased BUT in such patients. They did not observe any correlation between BUT and palpebral fissure width. Prause et al. (1987) reported that increased blink frequency is an incomplete compensation for decreased BUT. Our observations of decreased BUT with high blink rate corroborate the views of Prause et al. (1987). In the present study the Schirmer-Itest value in controls and Graves’ ophthalmopathy patients 348
were well above the cut off value of 10 mm/5 min (Jones 1966), thus indicating normal tear secretion. Similar observations have been made by Gilbard & Farris (1983). The mean rose bengal staining intensity score in early (0.66 f 1.1) as well as late (4.53 f2.29) Graves’ ophthalmopathy patients was significantlyhigh (P < 0.05 and < 0.001, respectively) as compared to controls (0.16 f0.37). Lissamine green score was almost identical to rose bengal (Table 2). Gilbard & Farris (1983) also observed a high rose bengal score. Using multiple regression analysis, they found a strong relationship between palpebral fissure width and rose bengal staining. They further reported that blink rate also contributed significantly to predict rose bengal staining, higher blink rates were associated with higher rose bengal staining scores. They also concluded that exophthalmos, lagophthalmos and lid lag did not contribute significantlyto predict rose bengal staining which had inverse relation with BUT. Due to limited material, no attempt was made to find out statistical correlation between the different parameters studied. Our observations (Table 3), reveal that the incidence of dry eye in Graves’ ophthalmopathy is quite high. Therefore, in each patient tear film profile should also be studied along with the thyroid status and ocular examination during each follow-up so that appropriate measures in the form of artificial tears etc. can be taken well in time. Gilbard & Farris (1983) suggested that tear film osmolarity is raised not only in patients with keratoconjunctivitis sicca, but in Graves’ ophthalmopathy also and thus should always be estimated
in such patients. However, we conclude that studying tear film profile and grading each patient for dry eye as described by Khurana et al. (1991) is quite informative, easy and reproducible.
References Fox S A (1966): The palpebral fissure. Am J Ophthalmol 62: 73-78. Gilbard J P & Farris R L (1983): Ocular surface drying and tear film osmolarity in thyroid eye disease. Acta Ophthalmol (Copenh) 61: 108-116. Jones L T (1966): The lacrimal secretory system and its treatment. Am J Ophthalmol62: 47-60. Khurana A K, Chaudhry R, Ahluwalia B K & Gupta S (1991): Tear film profile in dry eye. Acta Ophthalmol (Copenh) 69: 79-86. Moudgil S S, Khurana A K, Singh M et al. (1989): Tear film flow and stability in normal Indian subjects. Indian J Ophthalmol37 (4): 182-183. Perlmutter J C, Burde R M, Gad0 M & Roper-Hall G (1977):Endocrine ophthalmopathy: a disease wearing
many masks. In: Glaser J S (ed). Neuro-ophthalmology (Symp Univ Miami and Bascom Palmer Eye Inst), Vol 9, pp 160-176. C.V. Mosby, St. Louis. Prause J et al. Relation between blink frequency and break up time. Acta Ophthalmol (Copenh) 65: 19-22. Werner S C (1969): Classification of the eye changes of Graves' disease: Am J Ophthalmol 68: 646-648. Werner S C (1971): Ocular manifestations: Introduction. In: Werner S C & Ingbar S H (eds). The Thyroid A Fundamental and Clinical Text, 3rd edn, pp 528-533. Harper & Row, New York. Whitcher J P (1987): Clinical diagnosis of the dry eye. In: Smolin G & Friedlaender M H (eds),The Dry Eye. Int Ophthalmol Clin 27(1): 7-24.
Received on January 13th, 1992. Author's address:
Dr A. K. Khurana, 34/95 - Medical Enclave, Rohtak-124001, Haryana, India.
349
70 (19921 346-349
Tear film profile in Graves’ ophthalmopathy A. K. Khurana’, Sham Sunder’, B. K. Ahluwalia’ and K. C. Malhotra2 Departments of Ophthalmology’and Medicine‘, Medical College & Hospital, Rohtak, India
Abstract. Tear film profile was studied in 30 patients with Graves’ ophthalmopathy.Tear film pH, fluorescein staining, marginal tear strip and Schimer test values in patients with Graves’ ophthalmopathywere comparable with controls,indicating normal tear secretion. Tear film break-up-time (BUT) in late Graves’ ophthalmopathy was significantlylow suggesting unstable tear film. Rose bengal as well as lissamine green staining intensity scores were signiGcantly high, indicating presence of drying epithelial cells in early as well as late Graves’ ophthalmopathy patients. Key words: Graves’ ophthalmopathy - tear film - dry eye.
Patients with Graves’ ophthalmopathy frequently have symptoms of ocular surface discomfort strikingly similar as to those found in dry eye (Perlmutter et al. 1977; Werner 1971). The drying of ocular surface has been attributed to corneal exposure (Perlmutter et al. 1977; Werner 1971). Increased palpebral fissure width in patients with Graves’ ophthalmopathy may accelerate tear f ilm evaporation (Gilbard & Farris 1983). Tear film profile was studied in detail in the present work in order to comment on frequency, pattern and pathophysiology of ocular surface drying in Graves’ ophthalmopathy.
Material and Methods The present study was undertaken in 30 randomly selected cases of Graves’ophthalmopathy. Patients
346
with other associated conditions leading to abnormalities of tear film flow and/or stability and those using artificial tears were not included in the study. Each patient conformed to one of the classes of Graves’ ophthalmopathy as classified by American Thyroid Association (ATA) (Werner 1969), irrespective of the hormonal status. For the purpose of analysing the results, cases were divided into early (ATA-class 1 and 2) and late Graves’ ophthalmopathy (ATA-class 3 to 6). In each patient the width of palpebral fissure was measured as described by Fox (1966) and number of blinks per minute were counted using the sham of palpating the radial pulse. Exophthalmometry was carried out in erect position using Hertel’s exophthalmometer. Tear film profile was studied in detail as described elsewhere (JShurana et al. 1991). In addition, 30 age and sex matched controls also underwent similar investigations.The results were computed and analysed.
Results Out of 30 patients with Graves’ ophthalmopathy, 18 were females and 12 males with a female-male ratio of 1.5:l. The mean age was 32.73 k9.42 (range 17-50 years). The controls were age (mean 33.53 k 9.71, range 18-50) and sex (16 females and 14 males) matched. In accordance with thyroid status, 19 (63.33%)were hyperthyroid and 11 (36.67%)euthyroid. None of the patients had hypothyroidism.
Group
Control Early Graves’ ophthalmopathy Late Graves’ ophthalmopathy
No. of subjects
Exophthalmometry readings (in mm)
30 15 15
All the controls were euthyroid. Fifteen patients each were with early and late Graves’ ophthalmopathy. The mean palpebral fissure width noted in controls and patients with early and late Graves’ ophthalmopathy was 10.6 f 0.91, 12.4 f 1.50, and 14.53 f 1.55 mm, respectively.The mean blink rate was 14.26 f 3.31 in controls and 15.33 k 4.92 and 15.26 f8.94 in patients with early and late Graves’ ophthalmopathy,respectively.Exophthalmometry readings in patients with Graves’ ophthalmopathy and controls are shown in Table 1. The values of different tear function tests in patients with early
Right eye
Left eye
15.06 f 1.38 16.0 f 1.81 20.1 52.53
15.23 f 1.33 16.13 f 1.59 19.8 f 2 . 6 2
and late Graves’ ophthalmopathy and controls are depicted in Table 2. Distribution of patients, based on tear film profile, into different grades according to Khurana’s criteria (1991) is shown in Table 3.
Discussion Drying of ocular surface in Graves’ ophthalmopathy is thought to result from exposure attributed to upper lid retraction, exopathalmos, lagophthalmos,inability to elevate the eyes and a de-
Graves’ ophthalmopathy patients S. No.
Tear function tests
Early (n: 15)
Late (n: 15)
Controls (n: 30)
347
Table 3. Distribution of cases into different grades of d r y eye (Khurana et al. 1991).
Number of cases (per cent) Grade of dry eye
Total score
Graves’ ophthalmopathy patiens Controls Early
No dry eye Dry eye suspect Mild dry eye Moderate dry eye Severe dry eye
creased blink rate (Perlmutter et al. 1977; Werner 1971). An attempt has been made in the present study to comment on the tear film profile in patients with Graves’ophthalmopathy. Mean palpebral fissure width was significantly high in early as well as late Graves’ ophthalmopathy cases. Similar observations have been made by other workers (Gilbard& Farris 1983).It can be attributed to lid retraction and exophthalmos. Stellwag‘s sign, i.e. infrequent blinking, in Graves’ ophthalmopathy is in contrast to high blink rate noted in the present study. Gilbard and Farris (1983)also noted increased blink rate and consider it due to increased ocular surface irritation. A scanty,discontinousor absent tear meniscus is an important sign of dry eye (Whitcher 1987). None of the patients with Graves’ophthalmopathy had discontinuous or absent tear strip in the present study. The values of BUT observed in early Graves’ ophthalmopathy patients (12.21 f 2.09) were comparable with controls (12.42 f 2.55 sec), whereas in late Graves’ ophthalmopathy BUT (6.61 f 2.79) was significantly less ( P < 0.001) than the controls and reported cut off point of 10 seconds in an Indian population (Moudgilet al.1989). Gilbard & Farris (1983)also found decreased BUT in such patients. They did not observe any correlation between BUT and palpebral fissure width. Prause et al. (1987) reported that increased blink frequency is an incomplete compensation for decreased BUT. Our observations of decreased BUT with high blink rate corroborate the views of Prause et al. (1987). In the present study the Schirmer-Itest value in controls and Graves’ ophthalmopathy patients 348
were well above the cut off value of 10 mm/5 min (Jones 1966), thus indicating normal tear secretion. Similar observations have been made by Gilbard & Farris (1983). The mean rose bengal staining intensity score in early (0.66 f 1.1) as well as late (4.53 f2.29) Graves’ ophthalmopathy patients was significantlyhigh (P < 0.05 and < 0.001, respectively) as compared to controls (0.16 f0.37). Lissamine green score was almost identical to rose bengal (Table 2). Gilbard & Farris (1983) also observed a high rose bengal score. Using multiple regression analysis, they found a strong relationship between palpebral fissure width and rose bengal staining. They further reported that blink rate also contributed significantly to predict rose bengal staining, higher blink rates were associated with higher rose bengal staining scores. They also concluded that exophthalmos, lagophthalmos and lid lag did not contribute significantlyto predict rose bengal staining which had inverse relation with BUT. Due to limited material, no attempt was made to find out statistical correlation between the different parameters studied. Our observations (Table 3), reveal that the incidence of dry eye in Graves’ ophthalmopathy is quite high. Therefore, in each patient tear film profile should also be studied along with the thyroid status and ocular examination during each follow-up so that appropriate measures in the form of artificial tears etc. can be taken well in time. Gilbard & Farris (1983) suggested that tear film osmolarity is raised not only in patients with keratoconjunctivitis sicca, but in Graves’ ophthalmopathy also and thus should always be estimated
in such patients. However, we conclude that studying tear film profile and grading each patient for dry eye as described by Khurana et al. (1991) is quite informative, easy and reproducible.
References Fox S A (1966): The palpebral fissure. Am J Ophthalmol 62: 73-78. Gilbard J P & Farris R L (1983): Ocular surface drying and tear film osmolarity in thyroid eye disease. Acta Ophthalmol (Copenh) 61: 108-116. Jones L T (1966): The lacrimal secretory system and its treatment. Am J Ophthalmol62: 47-60. Khurana A K, Chaudhry R, Ahluwalia B K & Gupta S (1991): Tear film profile in dry eye. Acta Ophthalmol (Copenh) 69: 79-86. Moudgil S S, Khurana A K, Singh M et al. (1989): Tear film flow and stability in normal Indian subjects. Indian J Ophthalmol37 (4): 182-183. Perlmutter J C, Burde R M, Gad0 M & Roper-Hall G (1977):Endocrine ophthalmopathy: a disease wearing
many masks. In: Glaser J S (ed). Neuro-ophthalmology (Symp Univ Miami and Bascom Palmer Eye Inst), Vol 9, pp 160-176. C.V. Mosby, St. Louis. Prause J et al. Relation between blink frequency and break up time. Acta Ophthalmol (Copenh) 65: 19-22. Werner S C (1969): Classification of the eye changes of Graves' disease: Am J Ophthalmol 68: 646-648. Werner S C (1971): Ocular manifestations: Introduction. In: Werner S C & Ingbar S H (eds). The Thyroid A Fundamental and Clinical Text, 3rd edn, pp 528-533. Harper & Row, New York. Whitcher J P (1987): Clinical diagnosis of the dry eye. In: Smolin G & Friedlaender M H (eds),The Dry Eye. Int Ophthalmol Clin 27(1): 7-24.
Received on January 13th, 1992. Author's address:
Dr A. K. Khurana, 34/95 - Medical Enclave, Rohtak-124001, Haryana, India.
349
