Investigation of parameters influencing intraocular pressure increases during sleep

In previous studies, we have observed that young normal subjects show an increase in intraocular pressure (IOP) after sleep. Here we describe three experiments which investigated: (i) the effects of sleep in five groups of subjects: glaucoma, suspect glaucoma, young high-normal IOP, old high-normal IOP groups and an elderly control group, (ii) the effect of exposure to bright light (2500 lux) during sleep on associated IOP changes, and (iii) the relationship between changes in IOP and plasma melatonin during sleep, For all experiments IOP was measured before and after sleep. We found that IOP increased significantly after sleep. There was also a significant difference between the five groups with the old high-normal group showing the greatest increase, and the young high-normal group showing the lowest increase in IOP. The increase in IOP after sleep was reduced when the same subjects slept in bright light compared to that recorded when subjects slept in the dark. Plasma melatonin levels, as well as IOP, increased after sleep in the dark although there was no correlation between these changes for individual subjects.     

IOP elevation in different phases of sleep

Large and significant increases in intraocular pressure (IOP) have previously been demonstrated after as little as 30 minutes of sleep.¹² The present experiment tests the hypothesis that the lack of eye movements during sleep is responsible for this increase in IOP. Nine subjects slept in the laboratory on two separate nights. IOP was measured (with subjects in the supine position) using a Keeler Pulsair noncontact tonometer. Eye movements were monitored using electro-oculography. Subjects were woken from sleep after 60–90 minutes, on one night when they were in rapid eye movement (REM) sleep, and on one night when they were not. IOP increased significantly on both nights, but the differences between these increases was not significant. Thus, mechanical factors associated with lack of eye movements do not appear to contribute to the increase in IOP after sleep.     

Fluctuations in intra-ocular pressure with sleep:I. Time course of IOP increase after the onset of sleep

Ten normal subjects slept over a series of four nights for time periods of 30 minutes, 1, 2 and 4 hours. Intra-ocular pressure (IOP) measurements were made using a non-contact tonometer before and after sleep. The subjects showed a significant increase in IOP of 3.45 mm Hg after 30 minutes of sleep and a further IOP increase thereafter to 6.41 mm Hg above baseline. Such increases in IOP after sleep in normal subjects suggest that glaucoma patients and those suspected of having glaucoma should be monitored overnight to assess their IOP control mechanisms.     

Nocturnal elevation of intraocular pressure is detectable in the sitting position

PURPOSE. When intraocular pressure (IOP) was monitored in supine healthy young adults throughout a 24-hour period, a diurnal-to-nocturnal elevation of IOP was observed. This study was undertaken to investigate whether a similar elevation of IOP can be detected when experimental subjects are in the sitting position. METHODS. Experimental subjects were 16 nonsmoking, healthy young volunteers (ages, 18-25 years). Subjects with myopia of more than 3 D were excluded. They were housed in a sleep laboratory for 24 hours in a strictly controlled environment. An 8-hour nocturnal/sleep period was assigned to each volunteer according to the individual's accustomed sleep cycle. IOP was measured every 2 hours with a pneumatonometer with the volunteers in both sitting and supine positions. Mean diurnal-to-nocturnal IOP change and the cosine-fit 24-hour IOP rhythm were compared between the sitting and the supine IOP data. RESULTS. Mean IOP was significantly higher in the nocturnal period than in the diurnal/wake period for both the sitting and the supine IOPs. The 24-hour IOP troughs appeared at the end of the diurnal period, and the peaks appeared at the end of the nocturnal period. The difference between the trough and the peak was 3.8 +/- 0.6 mm Hg (mean +/- SEM) in the sitting position and 3.4 +/- 0.6 mm Hg in the supine position. Cosine-fitting of 24-hour IOP data showed a synchronized 24-hour rhythm of the sitting and the supine IOPs for the group. There was no difference in the phase timing or the magnitude of variation between these two 24-hour rhythms of sitting and supine IOPs. CONCLUSIONS. A nocturnal elevation of IOP can be detected in healthy young adults in both the sitting and the supine positions. There is a 24-hour rhythm of sitting IOP that is not different from the 24-hour rhythm of supine IOP.     

Fluctuations in intra-ocular pressure with sleep:

Intra-ocular pressure (IOP) was measured immediately after normal subjects were woken from at least 5 hours sleep. Measurements were made at approximately 15 s intervals, for about 20 minutes. The IOP of all 14 subjects was elevated after sleep and returned to baseline levels with a time course which was approximately exponential; the longest time constant of return of IOP to baseline was 1056.9 s, and the shortest 133.5 s. Mean time constant of recovery was 404.8 s. The decrease in IOP may be related to melatonin levels which increase during sleep and decrease in the light, or be related to accommodation and eye movements which may act to 'pump' aqueous from the eye.     

Twenty-four-hour time course of intraocular pressure in healthy and glaucomatous Africans: relation to sleep patterns

OBJECTIVE: The study was performed in early middle-aged African natives with primary open-angle glaucoma to compare the 24-hour intraocular pressure (IOP) variations in healthy versus young glaucoma patients, because IOP follows a circadian (24-hour) oscillation in healthy Caucasians. DESIGN: Case-control study. PARTICIPANTS: Sixteen healthy African volunteers (age 24.5 +/- 1 years, mean +/- standard error of the mean) and 11 open-angle glaucoma African patients (age 36.2 +/- 3.3 years). METHODS: IOP was measured hourly during 24 hours with a Modular One pneumatonometer (Modular One, Digilab, Cambridge, MA), which allows measures in supine subjects. To allow the IOP measurement at night, subjects were awakened under polysomnography (electroencephalogram, electromyogram, electro-oculogram) recorded at night and during a 90-minute afternoon nap. MAIN OUTCOME MEASURES: Hourly IOP values were analyzed for circadian rhythmicity with the Cosinor technique and in relation to the state of wakefulness, light sleep (stages 1 and 2), slow-wave sleep (stages 3 and 4), and rapid eye movement (REM) sleep upon awakening. RESULTS: Sleep patterns did not differ between patients and healthy volunteers. As expected, in the healthy subjects, IOP followed a 24-hour rhythm with a nocturnal peak value (acrophase), and the variations in IOP during sleep were related to sleep structure, being lowest during REM sleep and highest during slow-wave sleep. In the glaucoma patients, however, the 24-hour rhythm of IOP was reversed, with an afternoon acrophase and an early morning trough. CONCLUSIONS: These data suggest a circadian phase shift in IOP in glaucoma patients, with maintained relation to sleep structure.     

Association of central corneal thickness and 24-hour intraocular pressure fluctuation

PURPOSE: To evaluate the association between office-hour central corneal thickness (CCT) and 24-hour intraocular pressure (IOP) fluctuation in patients with glaucoma. DESIGN: Observational case-control study. METHODS: Measurements of IOP were obtained every 2 hours during a 24-hour period from 52 untreated glaucoma patients and 29 age-matched normal control subjects housed in a sleep laboratory. Habitual IOP measurements were obtained using a pneumatonometer in the sitting positions during the diurnal/wake period (7 AM to 11 PM) and in the supine position during the nocturnal/sleep period (11 PM to 7 AM). CCT was measured in all subjects using ultrasound pachymetry once during office hours. The association between IOP fluctuation (peak IOP-trough IOP) during the 24-hour period and the office-hour CCT was assessed in both glaucoma patients and healthy age-matched controls using Spearman rank order correlation. RESULTS: There was no statistically significant correlation between IOP fluctuation and CCT in glaucomatous (P=0.405) and normal subjects (P=0.456). CONCLUSIONS: Twenty-four-hour IOP fluctuations were not correlated with single CCT measurements taken during office hours in glaucoma patients.     

Twenty-four-hour pattern of intraocular pressure in young adults with moderate to severe myopia

PURPOSE: To characterize the 24-hour change of intraocular pressure (IOP) in young adults with moderate to severe myopia. METHODS: Nineteen young adults, ages 18 to 25 years, with moderate to severe myopia (myopia group) and 17 age-matched volunteers with emmetropia or mild myopia (control group) were housed for 1 day in a sleep laboratory. An 8-hour accustomed sleep period was assigned to each volunteer. Twelve measurements of IOP, axial length, blood pressure, and heart rate were taken at 2-hour intervals. In the wake period, blood pressure and heart rate were measured after a 5-minute bed rest. Axial length and IOP were measured in supine volunteers. Volunteers then sat for 5 minutes, after which IOP was measured. In the sleep period, measurements were taken in supine volunteers in bed. RESULTS: In both the myopia and control groups, the average supine IOP in the sleep period was higher than the average sitting IOP in the wake period. However, the magnitude of this IOP elevation at night was significantly less in the myopia group. In the sleep period, IOP was less in the myopia group than in the control group. When only the 24-hour supine IOP data were considered, the trough occurred at 1:30 AM, and the peak occurred around noon in the myopia group. In the control group, the trough was at 9:30 PM, and the peak at 5:30 AM. Least-square cosine fits showed 24-hour rhythms of supine IOP in both groups, but their phase timings were different. Axial length remained unchanged throughout the day and night in both groups. There was no difference in the 24-hour rhythms of mean blood pressure and heart rate between the two groups. CONCLUSIONS: Considering habitual body positions, IOP increases at night in young adults with moderate to severe myopia, but the magnitude of the increase is significantly less than that in the age-matched control subjects. There is a 24-hour rhythm of supine IOP in the myopic group, but the phase timing is different from that in the control subjects. These variations of IOP in young adults with moderate to severe myopia are not related to changes in cardiovascular parameters.     

Correlation between office and peak nocturnal intraocular pressures in healthy subjects and glaucoma patients

PURPOSE: To evaluate the correlations between office-hour intraocular pressures (IOP) and peak nocturnal IOP in healthy and glaucomatous eyes. DESIGN: Retrospective review of laboratory records. METHODS: We reviewed 24-hour data of IOP collected from 33 younger healthy subjects (aged 18 to 25 years), 35 older healthy subjects (aged 40 to 74 years), and 35 untreated older glaucoma patients (aged 40 to 79 years) housed in a sleep laboratory. Measurements of IOP were taken every 2 hours using a pneumatonometer in the sitting and supine positions during the diurnal/wake period (7 AM to 11 PM) and in the supine position during the nocturnal/sleep period. Correlations between average sitting or supine IOP in the right eye between 9:30 AM and 3:30 PM (office hours) and peak right eye IOP during the nocturnal hours were analyzed. RESULTS: The average values of supine IOP during office hours were found to have the strongest correlation with peak nocturnal IOP in older glaucoma subjects (r = .713, P < .001), whereas the correlation was less in older healthy subjects (r = .523, P < .01) and was absent in younger healthy subjects (r = .224, P = .21). The correlation between average sitting IOP values during office hours and peak nocturnal IOP was also strong in older glaucoma subjects (r = .601, P < .001) and moderate in older healthy subjects (r = .412, P < .05), but absent in younger healthy subjects (r = -.077, P = .672). CONCLUSION: Using a modification of the diurnal IOP curve, the magnitude of peak nocturnal IOP in untreated glaucoma patients can be estimated during routine office visits. Supine IOP measurements estimate peak nocturnal IOP better than sitting measurements. This estimation may provide the clinician with valuable information regarding the nocturnal IOP peak in glaucoma patients.     

Effects of head elevation on intraocular pressure in healthy subjects: raising bed head vs using multiple pillows

Purpose

To evaluate the effects of different methods of head elevation on intraocular pressure (IOP) in healthy young subjects.

Methods

Twenty-four healthy young Korean subjects were included in this prospective observational study. The IOP measurements were taken with the subjects in the sitting position and in the supine positions with the head flat and 30° up using two different methods: (1) raising the bed head and (2) using multiple pillows. IOP was measured using Tonopen AVIA in both eyes 10 min after assuming each position in a randomized sequence. The Wilcoxon signed-rank test was used to compare the IOP by changing the methods of head elevation.

Results

Mean IOP of both eyes when sitting was lower than that measured in the supine position with head flat (P=0.001). Compared with that measured in the supine position with head flat, the mean IOP was lower when measured in the supine position with the head kept 30 ° up by bed head elevation (P=0.001), whereas the mean IOP was not significantly different when measured in the supine position with the head elevated using multiple pillows (right eye, P=0.061; left eye, P=0.089).

Conclusion

In normal subjects, IOP was lower when measured in the supine position with the head kept up by the bed head elevation compared with that measured when lying flat. However, such head-up position-induced IOP reduction was not found when the head was kept up using multiple pillows. These findings suggest that elevating the head using multiple pillows may not help to reduce IOP in the supine posture.     

Diurnal variation of intraocular pressure and its correlation with retinal nerve fiber analysis in Turkish patients with exfoliation syndrome

Purpose The purpose was to evaluate the diurnal variation (DV) of intraocular pressure (IOP) in patients with exfoliation syndrome (XS), to measure retinal nerve fiber layer (RNFL) thickness by using scanning laser polarimetry, and to compare these measurements with those of normal subjects. Methods Forty-five subjects with XS and 40 healthy, age/sex matched subjects were recruited into the study. A detailed ophthalmologic examination was performed. IOP measurements were obtained at 08:00 am, 12:00 pm, 03:00 pm, and 06:00 pm. The XS group was further divided into DV ≥5 mmHg and DV<5 mmHg groups and also according to the existence of IOP fluctuation. The IOP measurements and RNFL thickness measurements were compared between the groups. Results The mean IOP value was found to be highest in the morning both in the XS and control groups. IOP showed a gradual decrease from 8.00 am to 6.00 pm in the control group, whereas a second peak at 03:00 pm was observed in the XS group. There was a fluctuation in 53.3% of the XS group, while none of the healthy subjects showed fluctuation. Superior and inferior ratios were statistically lower in XS patients than those in control subjects (p<0.05). Moreover, in patients with XS showing a DV ≥5 mmHg and/or a fluctuation, the superior ratio, inferior ratio, the number, superior average and superior integral were significantly different (all p values <0.05) from those of control subjects. Conclusions As the XS patients with high diurnal IOP variation and fluctuating pattern of IOP had lower RNFL thickness measurements, it is crucial to follow up these patients by performing scanning laser polarimetry in order to discover any possible glaucomatous damage at an earlier stage than with the use of conventional visual field analysis.     

佛司可林两个类似物对饮水导致的人眼压升高的影响

目的实验观察佛司可林两个类似物,即isoforskolin(isoF),deacetylforskolin(deaF),对饮水导致急性人眼压升高的影响.方法按随机双盲法设计,将佛司可林两个类似物配成的滴眼液分别滴人l眼,相应的溶媒滴入另眼.让受试者饮水(14 ml/kg)造成急性人眼压升高.给药前后用气动式眼压计测定眼压值,观察眼压变化.结果表明isoF(0.5%)及deaF(1.0%)均有抑制作用,最大抑制率分别为¨.4%及12.0%,并且副作用小.结论实验证明isoF(0.5%)及deaF(1.0%)抑制饮水导致急性人眼压升高.     

Risk factors for incident open‐angle glaucoma: a population‐based 20‐year follow‐up study

Purpose:  To study the effect of potential risk factors on the development of open‐angle glaucoma (OAG) in a population in which pseudoexfoliation (PEX) is a common finding. Methods: In 1984–1986, a population‐based survey of 760 people aged 65–74 years was conducted in the municipality of Tierp, Sweden. From 1988 to 2006, a follow‐up study of the 530 people with normal visual fields has been in progress. To increase the cohort, 273 ophthalmic outpatients were enroled. Reliable visual fields were available for 679 people, representing 6 126 person‐years at risk. A time‐weighted mean intraocular pressure (IOP) for all visits was calculated. Results: Sixty‐four subjects developed definite OAG, 29 of whom were exposed to PEX. Risk factors associated with OAG were higher age, a positive family history, increased IOP and PEX. The age‐standardized rate ratio (SRR) was 14.8 times (95% confidence interval [CI] 7.92–27.8) greater in subjects with mean IOP ≥20 mmHg than in those with mean IOP <20 mmHg. When subjects with IOP <20 mmHg at baseline were affected by PEX, the SRR increased 5.01‐fold (95% CI 1.97–12.8), compared with the unaffected group. However, when mean IOP at follow‐up was taken into account, there was no relationship between OAG and PEX as a distinct risk factor. Among participants in the population survey, 69% of all cases were attributable to a mean IOP ≥20 mmHg. Conclusion: Increased IOP and PEX were serious risk factors for incident OAG. The effect of PEX was mediated by increased IOP.     

The prevalence of glaucoma in patients with sleep apnea syndrome: same as in the general population

PURPOSE: An association of glaucoma and sleep apnea syndrome (SAS) has been widely reported. We investigated the largest group of patients with SAS thus far to determine the prevalence of glaucoma among these patients. DESIGN: Cross-sectional study. METHODS: An institutional study. STUDY POPULATION: A total of 228 patients with SAS. OBSERVATION PROCEDURES: Sleep studies determined the respiratory disturbance index (RDI) during night sleep. Ocular examination included intraocular pressure (IOP) measurement, optic disk evaluation, and Humphrey visual field examination. MAIN OUTCOME MEASURES: The SAS was diagnosed as an RDI > 10. The RDI was graded to determine the severity of SAS: mild (RDI, 10-19), moderate (RDI, 20-39), and severe (RDI > 40). Open-angle glaucoma was diagnosed when a glaucomatous visual field defect matched the optic disk changes, irrespective of IOP levels. RESULTS: Nineteen participants had mild SAS (mean +/- standard deviation, RDI = 15 +/- 3), 129 had moderate SAS (RDI = 28 +/- 5), and 80 had severe SAS (RDI = 54 +/- 11). Open-angle glaucoma was found in five SAS subjects, a prevalence of 2% (95% confidence interval, 0.7% to 5%). There was no correlation between RDI and the presence of glaucoma (chi-square = 1.18; degrees of freedom = 2; P =.6) or between the RDI and the IOP (r = -0.067; P =.316). CONCLUSION: The prevalence of glaucoma in SAS patients was similar to that in the general Caucasian population.     

Open-angle glaucoma and systemic hypertension: the blue mountains eye study

PURPOSE: To assess whether systemic hypertension is associated with open-angle glaucoma (OAG) in an older population. PATIENTS AND METHODS: The Blue Mountains Eye Study examined 3654 subjects aged 49 to 97 years. Hypertension was diagnosed from history in treated subjects or from systolic blood pressure (BP) > or=160 mm Hg or diastolic BP > or=95 mm Hg. OAG was diagnosed from congruous glaucomatous optic disc rim thinning and visual field loss, without reference to intraocular pressure (IOP) level. Ocular hypertension (OH) was defined when IOP was > 21 mm Hg in either eye, among persons without OAG. RESULTS: Hypertension was present in 45.7% of subjects, OAG in 3.0%, and OH in 5.2%. Hypertension was significantly associated with OAG, after adjustment for OAG risk factors including IOP, odds ratio (OR) 1.56, 95% confidence interval (CI) 1.01-2.40. This relation was strongest in subjects with poorly controlled treated hypertension (OAG prevalence 5.4%), compared with normotensive subjects (OAG prevalence 1.9%), independent of IOP (OR 1.88, CI 1.09-3.25). The population attributable risk for hypertension (20.4%) was higher than for other identified OAG risk factors. The prevalence of OH was 8.1% in subjects with poorly controlled treated hypertension (OR 1.81, CI 1.20-2.73) and 8.2% in untreated hypertension (OR 1.96, CI 1.31-2.95), compared with 4.2% in normotensive subjects. CONCLUSIONS: Hypertension, particularly if poorly controlled, appears related to a modest, increased risk of OAG, independent of the effect of BP on IOP and other glaucoma risk factors. However, we could not exclude nocturnal hypotensive episodes among treated subjects. Hypertension was also associated with OH, a relationship that could in part reflect the influence of BP on IOP.     

Study of follow-up period and provocative tests for diagnosis of primary open-angle glaucoma

How long should we follow up the patients with glaucomatous visual field defects to confirm the diagnosis of primary open-angle glaucoma (POAG)? What is the most important examination for the diagnosis of POAG? In order to answer these questions, 108 eyes of 60 cases were followed up for more than 4 years. All of these subjects presented both open angle and glaucomatous field defects. In the patients who did not present the increment of the intraocular pressure (IOP) within one month from the first visit, the relationship between the increment of IOP after one month and provocative tests, sex, age and refractions were evaluated. Of these, 47 eyes showed an increment of IOP within one month from the first visit. The other 61 eyes, suspected of low tension glaucoma (LTG), were followed up for the further course of IOP. Of these, 25 eyes showed an increment of IOP after one month to 6 years from the first visit, and the other 36 eyes did not for more than 4 years to 21 years. Follow-up for at least one year is necessary to confirm the diagnosis of POAG. In order to predict the increment of IOP in the subjects with normal IOP and glaucomatous field defects, the ratio Po/C after drinking water is the most sensitive examination.     

Relative change in diurnal mean ocular perfusion pressure: a risk factor for the diagnosis of primary open-angle glaucoma

PURPOSE: To investigate diurnal change and pattern of variation in intraocular pressure (IOP) and systolic (SBP) and diastolic (DSP) blood pressures in a group with untreated primary open-angle glaucoma (uPOAG) and compare it with an age-matched, normal group. METHODS: IOP, SBP, and DBP were measured in 14 patients with uPOAG and in 14 normal subjects, every hour between 7 AM and 10 PM and the mean ocular perfusion pressure (MOPP) was calculated. Mixed-effect linear models were used to analyze the repeated-measures data in which both fixed and random effects were included. The relative diurnal change was calculated as the percentage decrease from maximum. RESULTS: The uPOAG group had the higher IOP (P < 0.001) and lower MOPP (P = 0.025). There was a significant diurnal change in IOP, SBP, DBP, and MOPP in both groups (P < 0.001). The pattern of diurnal variation in IOP (P = 0.137), SBP (P = 0.569), and DBP (P = 0.937) was not significantly different between groups but was significantly different for MOPP (P = 0.040). MOPP and IOP were most similar at 7 AM and 1 PM. Postprandial hypotension was significant for SBP, DBP, and MOPP (P < 0.001), but not IOP (P = 0.388) in both groups. The relative change in MOPP was larger in the uPOAG group (38% vs. 26%, P < 0.001), but the change in IOP was similar (42% vs. 41%, P = 0.786). There was a significant effect of DBP on IOP over the course of the day in the uPOAG group (P = 0.011) but not in the normal group (P = 0.733). CONCLUSIONS: The relative diurnal change in IOP was similar in both uPOAG and normal subjects but MOPP showed a significant difference. MOPP significantly decreased after lunch, and was at its lowest in uPOAG at 7 AM, when IOP was at its highest. A significant association was found between diurnal DBP and IOP in uPOAG.     

Once-daily versus twice-daily levobunolol (0.5%) therapy. A crossover study.

The authors executed a two-period, randomized, double-masked, crossover study comparing once-daily to twice-daily levobunolol hydrochloride (0.5%) in 20 patients with elevated intraocular pressure (IOP). Modified diurnal curves were performed at four times for each study arm: baseline, day 1, day 14, and day 28. The mean diurnal corrected decrease in IOP from baseline ranged from 16% +/- 11% to 22% +/- 9% when the subjects were treated twice daily, and from 14% +/- 10% to 18% +/- 8% when the same subjects were treated once daily. At day 1, patients had a significantly greater IOP lowering after twice-daily therapy than after once-daily therapy (P less than 0.05). At 14 and 28 days, there was no clinically significant difference between the two treatment regimens. The results of our crossover study suggest that once-daily treatment with levobunolol (0.5%) is as effective as twice-daily treatment.     

Long term effect of apraclonidine.

AIMS--To evaluate the effect of the chronic use of apraclonidine 0.5% on the intraocular pressure (IOP) of patients with glaucoma; also, to study the side effect profile of this drug when used chronically. METHODS--All patients who had uncontrolled IOP, who were either already on glaucoma medications, or who were intolerant of other glaucoma medications were enrolled. A total of 185 patients were started on apraclonidine 0.5% two to three times a day in one eye. RESULTS--Follow up extended to 35 weeks. The mean difference in IOP between treated and control eyes was 2.1 (SD 5.0) mm Hg. A similar IOP lowering effect was obtained comparing IOP difference from baseline in the treated eye only. CONCLUSION--By the end of the follow up period, 46% of patients were still on the medication. The drug was stopped in 23% of patients because of side effects and in 31% of patients because of failure to lower IOP significantly.     

The relationship between plasma MMP-9 and TIMP-2 levels and intraocular pressure elevation in diabetic patients after intravitreal triamcinolone injection

PURPOSE: To find out the relationship between steroid-induced intraocular pressure (IOP) rise and the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-2 (TIMP-2) in diabetic patients who underwent intravitreal triamcinolone acetonide (IVTA) injection for the treatment of diabetic macular edema. SUBJECTS AND METHODS: A total of 34 patients with diabetic macular edema who were treated with IVTA and 17 healthy subjects who served as control group for plasma MMP and TIMP levels were participated. Before IVTA treatment, patients and control subjects underwent complete ophthalmologic examination, including best-corrected visual acuity, slit-lamp biomicroscopy, IOP measurement with Goldmann applanation tonometry, and indirect ophthalmoscopy; and peripheral blood samples were collected from each study participants. Plasma levels of MMP-9, TIMP-2, and HbA1c levels were measured. Patients were seen 1, 6, 12, and 24 weeks after treatment and then every 6 months for up to 1 year for probable IOP rise. Patients were divided into 2 groups as having nonproliferative or proliferative diabetic retinopathy. These 2 groups were further classified according to their IOP levels as normal or elevated IOP (>21 mm Hg). RESULTS: The mean age of diabetic group of patients (n=34) and healthy control subjects (n=17) were 57.6+/-10.2 years (range: 22 to 70 y) and 53.1+/-10.3 years (range: 29 to 68 y), respectively. Seventeen (50%) diabetic patients had developed elevated IOP after a mean 2.2 months after IVTA injection. MMP-9 and TIMP-2 levels were found to be significantly higher in the diabetic groups with and without elevated IOP when compared with control group (P<0.001). MMP-9/TIMP-2 did not change significantly among the groups. Logistic regression analysis showed that only higher plasma TIMP-2 levels increase the risk of IOP elevation after IVTA injection in proliferative diabetic retinopathy (odds ratio=1.06, P<0.05). No significant relationship was found between IOP rise and HbA1c levels. CONCLUSIONS: The high levels of TIMP in diabetic patients might have a role on steroid-induced IOP rise. The key pathogenetic events that up-regulate TIMP levels should be investigated in steroid IOP rise in diabetics.