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   Table of Contents      
Year : 2005  |  Volume : 53  |  Issue : 4  |  Page : 243-247

A comparison of the circadian rhythm of intraocular pressure in primary chronic angle closure glaucoma, primary open angle glaucoma and normal eyes

1 Dr. Rajendra Prasad Centre for ophthalmic science, All India Institute of Medical Science, New Delhi, India
2 Department of Biostatistics, All India Institute of Medical Science, New Delhi, India

Correspondence Address:
Ramanjit Sihota
Dr. Rajendra Prasad Centre for ophthalmic science, All India Institute of Medical Science, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0301-4738.18905

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Purpose: To evaluate the circadian rhythm of intraocular pressure (IOP) in primary chronic angle closure glaucoma (PCACG), primary open angle glaucoma (POAG), and normal eyes.
Cross-sectional study of newly diagnosed patients of POAG (60 eyes), PCACG following laser iridotomy (75 eyes), and age and sex matched normal controls (75 eyes). All subjects underwent applanation tonometry at 7 a.m., 10 a.m., 1 p.m., 4 p.m., 7 p.m., and 10 p.m. by a masked observer. Circadian rhythms were classified based upon the timing and presence of peak pressure.
Age and gender in all three groups were comparable. Diurnal IOP fluctuations were significantly higher in PCACG (7.69 + 3.03 mmHg) and POAG (8.31 + 2.58 mmHg) groups compared to normal controls (4.83 + 2.46 mmHg). PCACG eyes and controls had similarly timed circadian rhythms, with PCACG eyes having a consistently higher IOP. At 7 and 10 a.m., IOP peaked more often in POAG eyes compared to PCACG eyes. A plateau type of circadian rhythm was most common in normal eyes. The timing of peak IOP could be significantly correlated with the type of primary glaucoma examined.
Afternoon peaks were more common in postiridotomy PCACG eyes, similar to the rhythm in normal eyes. Morning peaks were more frequent in POAG eyes. Diurnal fluctuation > 6 mmHg, associated with an IOP of 21 mmHg or more was never seen in a normal eye.

Keywords: diurnal variation, intraocular pressure, primary open angle glaucoma, primary angle closure glaucoma.

How to cite this article:
Sihota R, Saxena R, Gogoi M, Sood A, Gulati V, Pandey R M. A comparison of the circadian rhythm of intraocular pressure in primary chronic angle closure glaucoma, primary open angle glaucoma and normal eyes. Indian J Ophthalmol 2005;53:243-7

How to cite this URL:
Sihota R, Saxena R, Gogoi M, Sood A, Gulati V, Pandey R M. A comparison of the circadian rhythm of intraocular pressure in primary chronic angle closure glaucoma, primary open angle glaucoma and normal eyes. Indian J Ophthalmol [serial online] 2005 [cited 2023 Feb 1];53:243-7. Available from: https://www.ijo.in/text.asp?2005/53/4/243/18905

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The pathophysiology of glaucoma is unclear. Intraocular pressure (IOP) is easily measurable and only treatable risk factor for the prevention of progressive glaucomatous field defects. Normal IOP varies with age, sex, time of day, season and position of the patient. Studies have reported the IOP variations in normal subjects primary open angle glaucoma (POAG) patients[1],[2],[3],[4],[5]and one study each in patients with acute and subacute angle closure glaucoma.[6],[7] However, to the best of our knowledge, no study has evaluated the diurnal fluctuation of IOP in primary chronic angle closure glaucoma (PCACG). The present study aims to evaluate the circadian rhythm of IOP in patients of POAG, PCACG after a patent laser iridotomy, and to compare them with that of age and sex matched normals from the same population.

  Materials and Methods Top

Consecutive, newly diagnosed cases of primary glaucoma, 40-70 years of age, presenting to our glaucoma service over 6 months form January to June 2002 were screened. Those fulfilling the following criteria were included in the study.

Patients were diagnosed to have POAG if the IOP on three random recordings made on different visits was found to be higher than 21 mmHg with Goldmann applanation tonometry, in the presence of open angles on gonioscopy, and characteristic optic nerve head and visual field changes of glaucoma.[8],[9] Cases of pseudoexfoliation glaucoma were eliminated from the study by gonioscopy and slit lamp examination of eye after pupillary dilatation.

Patients were diagnosed as having PCACG if a chronically raised IOP of over 21 mmHg, on at least three occasions was recorded, in the presence of optic nerve head and visual field changes characteristic of glaucoma.[7],[8] Patients, with an angle with peripheral anterior synechiae extending over at least 180° on indentation gonioscopy, were included in this group.

A control group of 75 normal persons, age and sex matched to the glaucoma groups, were included in the study. They had attended our out-patient department for a routine refractive correction. The inclusion criteria were IOP < 21 mmHg by three random applanation tonometry recordings taken on different visits open angles on gonioscopy and normal optic nerve head/and visual fields. Individuals with a family history of glaucoma were excluded from the 'control' group.

Exclusion criteria for all groups were any prior medical or surgical intervention for the control of IOP, any previous ocular surgery, any other intraocular disorder or any condition preventing reliable applanation tonometry or visual field assessment. None of the subjects were on any systemic or topical medication that could potentially have affected the IOP. The previous use of topical or systemic steroids was specially asked for. Informed consent was taken from all individuals.

All diagnosed cases of PCACG underwent a Neodymium YAG laser iridotomy. Postlaser, a course of acetazolamide tablets 250 mg 8 hourly, and steroid drops were prescribed for 5 days. The circadian rhythm was evaluated 1 week after stopping acetazolamide. The circadian rhythm of IOP in all the three groups was measured after admission to the hospital. Goldmann applanation tonometry was carried out at 7 a.m., 10 a.m., 1 p.m., 4 p.m., 7 p.m. and 10 p.m. by a single experienced masked observer. At all points ± 15 min was permitted for the recording of IOP. There were no missing data points for any of the cases or controls. Each patient's circadian rhythm was classified as having one of the following patterns - morning peak, noon peak, night peak or a plateau pattern on the basis of timing of the peak pressures recorded in that diurnal curve. The diurnal curves were classified as 'morning' type, if the trough to peak difference in IOP of > 2 mmHg was recorded with peak at 7 or 10 a.m., 'afternoon' type, if recorded at 1 or 4 p.m., and 'night' type, if peak occurred at 7 or 10 p.m. A plateau type of circadian rhythm was defined as having an IOP difference of £ 2 mm between the maximum and minimum IOP.

Statistical analysis of one eye of each patient was performed. If both eyes met the relevant criteria, only the right eye was analysed. The statistical tests applied were one-way analysis of variance, followed by Scheffe's multiple range tests and Chi-square test of independence. The software used was Stata Version 7.0 programme.

  Results Top

There were 60 cases of PCACG, 75 cases of POAG and 75 normal persons enrolled in the study. The male to female ratio was 29: 31 in the PCACG group, 36: 39 females in POAG group and 37: 38 females in the normal subjects. The mean age was 57.64 ± 8.66 years in the normal subjects, 57.83 ± 9.33 years in the PCACG group and 57.38 ± 8.71 years in the POAG group. All the three groups were statistically similar with regard to age ( P = 0.95) and sex ( P = 0.83).

The mean IOP at all times during the day is listed in [Table - 1]. There was a statistically significant difference in the IOP levels at all points during the day for both PCACG and POAG when compared to normals ( P < 0.001). At 7 and 10 a.m., the POAG group showed a significantly higher IOP as compared to the PCACG group ( P < 0.01 ) . At all other times of the day, there was no significant difference in the IOP between these two groups.

The average peak IOP was 16.24 ± 2.61 mmHg for normals, 25.07 ± 3.60 mmHg for PCACG and 26.43 ± 3.28 mmHg for POAG cases [Table - 2]. Although the peak IOPs were significantly different when PCACG and POAG were compared to normal subjects ( P < 0.001), the difference between PCOAG and POAG eyes was not statistically significant ( P = 0.117). The range of IOP was 7-20 mmHg for normals, and 12-32 mmHg for both PCACG and PCACG cases.

The trough levels of IOP were 11.43 ± 2.11 mmHg in normals, 17.8 ± 2.84 mmHg in PCACG group and 18.35 ± 2.51 mmHg in POAG group [Table - 2]. There was a significant difference between PCACG and POAG eyes as compared to normals ( P < 0.001), but there was no significant difference between PCACG and POAG eyes.

The difference between the peak and trough IOP recorded in each diurnal curve was noted as the diurnal fluctuation. This range of diurnal fluctuation of IOP was 4.83 ± 2.46 mmHg in normals, 7.69 ± 3.03 mmHg in PCACG, and 8.31 ± 2.58 mmHg for the POAG group [Table - 3]. The fluctuation of diurnal IOP was significantly higher for the PCACG ( P < 0.001) and POAG ( P < 0.001) groups when compared to normals; the difference, however, was not significant when the PCACG and POAG groups were compared with each other ( P = 0.537).

A diurnal fluctuation in IOP of more than 8 mmHg was seen in 13.3% of normals, 30% PCACG and 38.6% of POAG eyes. However a variation of more than 6 mmHg was seen in 45.3% of normals, 85% chronic PCACG and 90.7% of POAG eyes. A diurnal fluctuation of 6-8 mmHg was seen significantly more frequently in the two primary glaucoma groups. None of normal eyes however had an IOP variation of >6 mmHg together with any reading of >21 mmHg [Table - 3]. [Table - 4] shows the sensitivity and specificity data for different limits of circadian variation.

[Table - 5] and [Figure - 1] show the distribution of the timing of the peak for normals and cases with a diagnosis of POAG or PCACG. The Chi-square test of independence for the contingency table drawn was significant ( P < 0.001). This indicates that the timing of the peak was associated with the diagnosis of the group. In an analysis of subgroups within the table the difference between normals and PCACG, with respect to the timing of peaks was not significant ( P = 0.1395). The distribution of peaks in POAG cases however differed significantly from both normals ( P = 0.0001) and PCACG cases ( P = 0.0018). The difference was significant even after correcting for the multiple tests of statistical significance used (Bonferroni method).[10] POAG cases had a higher proportion of morning peaks (51%) than PCACG cases (28%) and normals (31%). A plateau type of circadian rhythm formed a larger proportion (24%) of normal diurnal curves than either POAG (4%) or PCACG (10%) cases. The average IOP at the peaks recorded in the morning, afternoon and night, in the two glaucoma groups were similar [Table - 6].

  Discussion Top

A couple of decades ago, the treatment of PCACG was largely surgical, with the common predicament being, a choice of iridectomy alone or as part of a filtering surgery. With the introduction of laser iridotomy, the pathomechanism of repeated angle closure in PCACG is corrected noninvasively. Therefore, patients having PCACG today undergo a laser iridotomy initially, with an assessment for a chronically elevated IOP and appraisal of optic nerve head alongwith visual field changes. Knowledge of the circadian rhythm of IOP in PCACG eyes helps, both the diagnosis of PCACG after performing a laser iridotomy, and tailoring medications, i.e. their timings and the time of patient review to assess efficacy of therapy. Data on the degree of IOP fluctuation would also assist in determining therapy that would control the peak pressure in a given patient. To the best of our knowledge, no study has assessed the circadian rhythm of IOP in angle closure glaucoma eyes following a patent iridotomy.

PCACG eyes in our study showed more frequent afternoon peaks, a circadian rhythm that was akin to normal eyes, although with significantly higher levels of IOP. POAG eyes had more frequent peaks of IOP in the morning. A plateau type of IOP recording was more likely to be seen in normal eyes than in either of the glaucoma groups. Kimura noted a peak around noon in POAG eyes and night or early morning peaks in angle closure glaucoma.[3] Shapiro[7] documented the diurnal IOP in eyes of angle closure glaucoma without synechiae, which were probably cases of subacute primary angle closure glaucoma. This was done before an iridectomy was carried out, when he recorded midnight and morning peaks of pressure and a trough at 3 p.m. In 11 cases the diurnal IOP measurements were repeated after iridectomy and were found to be plateau like, similar to that of normal eyes in his study. The changed circadian rhythm in POAG could be related to other factors such as an altered plasma cortisol fluctuation as a factor of, or concomitant to POAG.

Katavisto[2] felt that afternoon recordings in POAG eyes were rarely maximal; we however found that 43.3% of PCACG and 17.3% peaks of POAG occurred in the afternoon. Kitazawa and Horie[11] found that an IOP recorded around noon correlated well with peak pressures.

The mean peak and trough values of IOP were alike in PCACG and POAG eyes, as was the range of IOP recorded during the day. Both differed significantly from normal eyes. This suggests that the pathophysiology leading to the rise in IOP was similar, as has been shown in histopathological studies of the trabecular meshwork in PCACG eyes.[12]

In our study, an IOP fluctuation of less than 6 mmHg was most likely in normal eyes but was present in 15% of PCACG and 9.3% of POAG eyes. All three groups had a significant number of eyes having an IOP fluctuation of 6-8 mmHg, more so the glaucoma groups. None of normal eyes however had an IOP variation of > 6 mmHg together with any reading > 21 mmHg. The generally held diagnostic criterion for POAG is an IOP variation of more than 8 mmHg, but this was absent in a significant number of glaucomatous eyes, both PCACG and POAG. Drance[13],[14] also noted a diurnal variation of IOP ranging between 5 and 9 mmHg in 28% of POAG eyes. Katavisto[2] suggested that a variation of more than 6.77 mmHg or an IOP of more than 23.4 mmHg should be considered pathological.

Katavisto[2] in his seminal work on diurnal variations suggested timings for such diurnal recordings to be 4 a.m., 6 a.m., 8 a.m., 10 a.m., 2 p.m., 6 p.m., and 10 p.m. There is considerable controversy about whether IOP recordings should be taken before getting out of bed or after, and the rapid changes of IOP that occur over the first 10-15 min on waking.[1] There is also concern whether such early morning measurements are physiological or have a significant autonomic overlay. We have therefore not included IOP measurements at 4 a.m. in our study.

In conclusion, PCACG eyes had mean peak and trough IOP values similar to POAG eyes. Afternoon peaks were more common in PCACG eyes after a laser iridotomy, similar to the circadian rhythm in normal eyes, and morning peaks were more frequent in POAG eyes. A diurnal fluctuation of more than 6 mmHg, associated with an IOP of 21 mmHg or more was never seen in a normal eye, and such eyes should be investigated thoroughly for either type of primary glaucoma.

  References Top

Frampton P, Darin D, Brown B. Diurnal variation of intraocular pressure and the overriding effects of sleep. Am J Optom Physiol Optics 1987;64:54-61.  Back to cited text no. 1
Katavisto M. The diurnal variations of intraocular tension in glaucoma. Acta Ophthalmol 1964;78:1-131.  Back to cited text no. 2
Leydhecker W. The intraocular pressure: Clinical aspects. Ann Ophthalmol 1976;8:389-99.  Back to cited text no. 3
Martin XD. Normal intraocular pressure in man. Ophthalmlogica 1992;205:57-63.  Back to cited text no. 4
Sacca SC, Rolando M, Marletta A, Macri A, Cerqueti P, Ciurlo G. Fluctuations of intraocular pressure during the day in open angle glaucoma, normal tension glaucoma and normal subjecys. Ophthalmologica 1998;212:115-9.  Back to cited text no. 5
Zeimer RC. Circadian variations in intraocular pressure. In : Ritch R, Shields MB, Krupin T, editors. The Glaucomas. St Louis, USA: Mosby; 1996. p. 429-45.  Back to cited text no. 6
Shapiro A, Zauberman H. Diurnal changes of the intraocular pressure of patients with angle closure glaucoma. Br J Ophthalmol 1979;63:225-7.  Back to cited text no. 7
Airaksinen PJ, Tuvlonen A, Werner EB. Clinical evaluation of thhe optic disc and retinal nerve fiber layer. In : Ritch R, Shields MB, Krupen T, editors. The Glaucomas. Philadelphia: W.B. Saunders Company: p. 617-58.  Back to cited text no. 8
Mickelberg FS, Drance SM. Glaucomatous visual field defects. In : Ritch R, Shields MB, Krupen T, editors. The Glaucomas. Philadelphia: W.B. Saunders Company; p. 523-37.  Back to cited text no. 9
Perneger TV. What's wrong with Bonferroni adjustments. BMJ 1998; 316:1236-8.  Back to cited text no. 10
Kitazawa Y, Horie T. Diurnal variation of intraocular pressure in primary open angle glaucoma. Am J Ophthalmol 1975;79:557-66.  Back to cited text no. 11
Sihota R, Lakshmaiah NC, Walia KB, Sen S, Jayalakshmi P, Agarwal HC. Ultrastructural changes in the trabecular meshwork of eyes with acute and chronic angle closure glaucoma. Indian J Ophthalmol 2001;49:255-60.  Back to cited text no. 12
Drance SM. The significance of the diurnal tension variations in normal and glaucomatous eyes. Arch Ophthalmol 1960;64:494-501.  Back to cited text no. 13
Drance SM. Diurnal variation of intraocular pressure in treated glaucoma: Significance in patients with chronic simple glaucoma. Arch Ophthalmol 1963;70:302-11.  Back to cited text no. 14


  [Figure - 1]

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]

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