Abstract
Purpose:
To investigate the incidence and risk factors for steroid-induced ocular hypertension (SI-OHT) in patients receiving intravitreal steroids for retinal inflammatory diseases.
Methods:
This retrospective observational study included patients who received either intravitreal triamcinolone acetonide (IVTA/TA group) or dexamethasone intravitreal implant (DEX group) for the management of retinal vascular diseases in the period of 2018–23. SI-OHT in those patients were followed up for 2 years. Steroid responders and nonresponders were characterized based on intraocular pressure (IOP) change from the baseline. The incidence, risk factors, and magnitude of IOP rise and its association with ocular and systemic illness were investigated.
Results:
Out of 1178 reviewed, 761 patients were excluded due to irregular follow-up. A total of 382 patients (382 eyes) who received either IVTA/DEX intravitreal implant during the study period were reviewed. The incidence of SI-OHT was found to be 46.3% (IVTA group) and 20.8% (DEX group) at 6 months, respectively. Among patients who received 2 mg IVTA dosage, 16.9% were steroid responders and 11.9% for the 4 mg group.
Conclusion:
We found that the incidence of SI-OHT was higher in IVTA group as compared to DEX group. No dose-dependent incidence was observed in the case of IVTA group. Age, gender, number of injections, and myopia were not associated with the risk of SI-OHT. Renal disease showed a significant association with the risk of SI-OHT in the DEX group, and patients with TB, stroke, and other drug allergies experienced a fivefold greater increase in IOP values in those groups.
Keywords: Dexamethasone, diabetic macular edema and risk factors, intravitreal triamcinolone acetonide, retinal vascular diseases, SI-OHT
Three synthetic steroids such as intravitreal triamcinolone acetonide (IVTA), dexamethasone (DEX) intravitreal insert, and fluocinolone acetonide implant have been in use in ophthalmology to treat posterior segment inflammatory diseases.[1] Off-label IVTA is approved by FDA for pars plana vitrectomy and for the treatment of posterior segment inflammatory disorders other than diabetic macular edema (DME) and retinal vein occlusion (RVO). However, this has been in use for many years for the treatment of retinal inflammatory diseases including DME, branched vein occlusion (BRVO), and central retinal vein occlusion (CRVO).[2,3,4] The biodegradable dexamethasone intravitreal insert is approved by FDA for the treatment of DME[5] noninfectious posterior segment uveitis,[6] and macular edema secondary to BRVO and CRVO.[7] Intravitreal implant of fluocinolone acetonide is yet another steroid approved by FDA for the treatment of chronic noninfectious posterior segment uveitis.[8]
A significant side effect of intravitreal steroid use is associated with the development of raised intraocular pressure (IOP) termed as steroid-induced ocular hypertension (SI-OHT), and it can progress to glaucoma (SIG) which may be severe. There are several studies in which elevated IOP has been documented following intravitreal steroid use, and the estimated incidence of SI-OHT after intravitreal steroid injection ranged from 11% to 79%.[9]
In India, the reported incidence of SI-OHT following IVTA was 27–50% and 17–26% with dexamethasone implant.[10,11] TA responders had more common early and severe IOP spikes compared to DEX administrations, and myopia was the most common risk factor for DEX-induced OHT.[11] In this study, the reported incidence of SI-OHT following intravitreal steroids is as a result of multiple injections received in both the eyes which might not reflect the true incidence of SI-OHT as it was not clear if the observed IOP spike was the result of multiple events or a consequence of an event after injection in one eye. Therefore, the present study was envisaged to investigate the incidence of SI-OHT and the risk factors for positive IOP response in patients receiving intravitreal steroids in one eye at a tertiary eye care clinic which will enable us to identify the true incidence of elevated IOP following intravitreal steroids.
Methods
Subjects and study setting
This retrospective observational study received approval from the Institutional Review Board (ID NO: RET202500503) and adhered to the Declaration of Helsinki. Data were collected from January 2018 to December 2023. The study included patients aged 18 and older diagnosed with diabetic macular edema (DME), retinal vein occlusion (RVO), central retinal vein occlusion (CRVO), or branch retinal vein occlusion (BRVO) who were treated with intravitreal IVTA or DEX implant injections at a tertiary eye care center. Only those patients who had received the intravitreal steroids for the first time and completed three consecutive visits after the intravitreal injection were included in the study, and patients with less than three consecutive visits and patients with prior intravitreal steroid injections history were excluded from the study.
Data collection and categorization of subjects
Goldmann applanation tonometry (GAT) was used to measure IOP, and baseline details were extracted from the hospital’s electronic medical records. The maximum follow-up duration for patients in the study was 2 years. Patients who received either a single or multiple intravitreal injections in one eye were included in the study. The difference between the IOP at the final visit and the baseline measurement was calculated. Patients with an increase of more than 5 mmHg were categorized as Steroid Responders (SR), while those with an increase of less than 5 mmHg were classified as Non-Responders (NR). Additionally, patients were further subclassified as moderate responders (with an increase of 6 to 15 mmHg) or severe responders (with an increase above 15 mmHg) based on their IOP changes following steroid treatment.[12]
Statistical analysis
Descriptive statistics, including mean (standard deviation) and frequency (percentages), were utilized to summarize the data. The normality of the data was assessed using the Kolmogorov–Smirnov test. A proportion test was employed to compare the percentages between the SR and NR groups. The Wilcoxon Signed-Rank test was used to compare continuous variables between the two groups. Logistic regression analysis was conducted, treating SR and NR as outcome variables. Additionally, a Cox proportional hazards regression analysis was carried out to evaluate the risk factors, such as age, sex, and systemic illness, in relation to OHT. A Kaplan–Meier survival curve was constructed to assess the survival rate of eyes over a 24-month period. A P value of less than 0.05 was considered statistically significant. The statistical analysis was performed using STATA Version 17 (Texas, USA) software.
Results
The total number of patients was 1178, of which 761 patients dropped out of the study due to irregular follow-up, and finally, 382 patients were included in the study. A total of 382 eyes of 382 patients who received IVTA and DEX intravitreal implant during the study period were reviewed. IVTA was administered to 260 patients (68%), while 122 patients (31.9%) received DEX implant. Among the TA group, the majority of the patients received 2 mg (77.3%) and the remaining received 4 mg (22.7%).
The baseline characteristics of the patients who received intravitreal steroid injections are presented in Table 1. The mean age of patients receiving IVTA injections and DEX implant was 59.02 ± 8.21 and 57.2 ± 10.22 years, respectively. Males constituted 56.2% in IVTA and 71% in DEX (P = 0.005). Among the IVTA patients, 65.4% received a single injection, while it was 71.3% for the DEX implant group. In BRVO patients, 35% received IVTA and 42.6% DEX; in DME, 41.9% IVTA and 33.6% DEX. In CRVO patients, both were used in similar proportions (23%). At final visit, AGM use was 7.7% in IVTA and 13.9% in DEX (P = 0.06) and especially beta blockers and its combination with brimonidine or carbonic anhydrase were prescribed to control the elevated IOP in those patients.
Table 1.
Baseline characteristics of patients/eyes with steroid treatment
| Parameters | TA group n=260 patients n (%) | DEX group n=122 patients n (%) | P |
|---|---|---|---|
| Number of injections (patients) | |||
| 1 2 3 |
170 (65.4) 88 (33.4) 2 (0.7) |
87 (71.3) 33 (27.1) 2 (1.64) |
0.249P 0.183P 0.436P |
| Injections (Months) | |||
| Time interval between first and last injections Mean±SD (Min-Max) |
4.32±4.57 (11 days – 40 months) |
4.93±3.98 (1 month -24 months) |
0.0036 R |
| Age (in years) | |||
| Mean±SD Range |
59.02±8.21 (37-86) |
57.2±10.22 (27-82) |
0.06T |
| Gender | |||
| Male Female |
146 (56.2) 114 (43.8) |
87 (71.3) 35 (28.7) |
0.005 C |
| Eye(s) | |||
| Right eye Left eye |
134 (51.5) 126 (48.5) |
68 (55.7) 54 (44.3) |
0.443C |
| Etiology | |||
| BRVO CRVO DME |
91 (35) 60 (23.1) 109 (41.9) |
52 (42.6) 29 (23.7) 41 (33.6) |
0.1512P 0.8812P 0.1207P |
| Need for AGM at final visit | |||
| No Yes |
240 (92.3) 20 (7.7) |
105 (86.1) 17 (13.9) |
0.06C |
| Systemic illness*P | |||
| Asthma Cardiac Diabetes Hyperlipidaemia Hypertension Nonocular surgery Renal Thyroid Others |
12 (2.2) 41 (7.42) 193 (34.9) 65 (11.77) 167 (30.25) 29 (5.25) 14 (2.53) 14 (2.53) 17 (3.1) |
4 (1.53) 22 (8.5) 85 (32.69) 33 (12.69) 84 (32.3) 6 (2.3) 12 (4.6) 6 (2.3) 8 (3.1) |
0.543 0.607 0.524 0.708 0.554 0.053 0.116 0.844 0.074 |
| Baseline IOP | |||
| Mean±SD (Min-Max) |
16.62±2.9 (8-21) |
16.63±2.78 (10-21) |
0.933R |
| Refractive error status | |||
| No Yes |
141 (54.2) 119 (45.7) |
65 (53.3) 57 (46.7) |
0.862C |
| Steroid responsiveness | |||
| Steroid Non-Responder (NR) Steroid Responder (SR) |
219 (84.2) 41 (15.8) |
98 (80.3) 24 (19.7) |
0.344C |
%, Column Percentage; *Some patients had more than one systemic illness; BRVO: Branch Retinal Vein Occlusion; CRVO: Central Retinal Vein Occlusion; DME: Diabetic Macular Edema; NR - <5 mmHg IOP increase at final visit; SR - >5 mmHg IOP increase at final visit; R-Wilcoxon rank sum test; P - Proportion Test; C – Chi-Square test; Boldface indicates statistical significance (P < 0.05)
Diabetes was the most common systemic illness observed in both steroid groups (34.9% in TA group and 32.69% in DEX), followed by hypertension at 30.25% and 32.3%, respectively. The mean IOP at baseline was similar in both groups (P = 0.933), and more than 80% of the patients in the TA and DEX implant groups were classified as steroid nonresponders. The incidence of SI-OHT in both TA and DEX implant groups was found to be 15.8% and 19.7%, respectively.
Also, the mean change in IOP was higher in the SR group for the IVTA injections (13.51 ± 10.52) when compared to DEX implant group (9.5 ± 3.91), though this was not significant (P = 0.2144). Additionally, the need for anti-glaucoma medication (AGM) at the final visit among SR was 48.8% in the IVTA group, while it was 71% in the DEX implant group (P < 0.01). We found that patients with renal diseases comprised nearly 9% of the SR group, compared to only 3% in the NR group for DEX implant (P = 0.048). No other systemic illnesses showed a significant association with OHT. Similarly, for DEX implant, in the SR group, 7.3% of patients had other conditions such as TB, stroke, and drug allergies, compared to 1.9% in the NR group (P = 0.042) [Table 2].
Table 2.
Characteristic features of eyes among SR and NR in steroid-treated groups
| Parameters | TA group NR n=219 Eyes | TA group SR n=41 Eyes | P | DEX group NR n=98 Eyes | DEX group SR n=24 Eyes | P | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean change in IOP, mm HG (Min-Max) |
-0.06±2.74 (-7 to 5) | 13.51±10.52 (6-64) | <0.0001 | 0.20±2.49 (-5 to 5) | 9.5±3.91 (6-22) | <0.0001 | ||||||
| Number of Injections | ||||||||||||
| 1 2 3 |
143 (65.3) 74 (33.8) 2 (0.9) |
27 (65.8) 14 (34.1) 0 |
0.95F | 70 (71.4) 27 (27.5) 1 (1.02) |
17 (70.8) 6 (25) 1 (4.2) |
0.553F | ||||||
| Age, years | ||||||||||||
| <=40 41-60 >=60 |
3 (1.4) 108 (49.3) 108 (49.3) |
2 (4.9) 23 (56.1) 16 (39.0) |
0.145F | 4 (4.1) 47 (47.9) 47 (47.9) |
2 (8.3) 14 (58.3) 8 (33.3) |
0.282F | ||||||
| Gender | ||||||||||||
| Male Female |
119 (54.3) 100 (45.6) |
27 (65.9) 14 (34.2) |
0.173C | 67 (68.4) 31 (31.6) |
20 (83.3) 4 (16.7) |
0.146C | ||||||
| Disease etiology | ||||||||||||
| BRVO CRVO DME |
77 (35.2) 49 (22.4) 93 (42.5) |
14 (34.2) 11 (26.8) 16 (39.0) |
0.817C | 48 (48.9) 20 (20.4) 30 (30.6) |
4 (16.7) 9 (37.5) 11 (45.8) |
0.015 C | ||||||
| Need for AGM at final visit | ||||||||||||
| No Yes |
219 (100) 0 |
21 (51.2) 20 (48.8) |
<0.001 C | 98 (100) 0 |
7 (29.2) 17 (70.8) |
<0.001 C | ||||||
| Systemic illnessP | ||||||||||||
| Asthma | 12 (2.63) | 0 | 0.135 | 3 (1.46) | 1 (1.82) | 0.849 | ||||||
| Cardiac | 36 (7.88) | 5 (6.02) | 0.557 | 17 (8.29) | 5 (9.1) | 0.850 | ||||||
| Diabetes | 161 (35.23) | 32 (38.5) | 0.561 | 65 (31.71) | 20 (36.36) | 0.513 | ||||||
| Hyperlipidemia | 56 (12.25) | 9 (10.84) | 0.716 | 30 (14.63) | 3 (5.45) | 0.069 | ||||||
| Hypertension | 144 (31.5) | 23 (27.71) | 0.491 | 69 (33.66) | 15 (27.27) | 0.368 | ||||||
| Nonocular surgery | 25 (5.47) | 4 (4.82) | 0.808 | 5 (2.44) | 1 (1.82) | 0.785 | ||||||
| Renal disease | 11 (2.41) | 3 (3.61) | 0.524 | 7 (3.41) | 5 (9.09) | 0.048 | ||||||
| Thyroid | 12 (2.63) | 2 (2.41) | 0.909 | 5 (2.44) | 1 (1.82) | 0.785 | ||||||
| Other systemic illness@ | 12 (2.63) | 5 (6.02) | 0.102 | 4 (1.95) | 4 (7.27) | 0.042 | ||||||
% Column Percentage; @- TB, Stroke, other drug allergies; C – Chi-square Test; F – Fisher’s Exact Test; P - Proportion Test; SR - Steroid Responder; NR: Non-Steroid Responder; Includes patients with multiple systemic illnesses; Boldface indicates statistical significance (P<0.05); Mean change in IOP for SR between TA and DEX groups was not significant (P=0.2144)
Among the IVTA group, 46% of the patients developed IOP rise within 3 months versus 62.5% with DEX. SI-OHT occurred in 46% of IVTA and 21% of DEX patients at 3–6 months (P = 0.0397). Moderate steroid response was more common with DEX (92% vs 66%, P = 0.0197), whereas severe response was higher with IVTA (34.2% vs 8.3%, P = 0.02). Among TA recipients, SR occurred in 16.9% with 2 mg and 11.9% with 4 mg [Table 3]. The hazard ratio was calculated for various independent variables concerning the significance of OHT. It was found that patients with systemic disease conditions such as tuberculosis (TB), stroke, and other drug allergies experienced a fivefold (HR = 5.71, 95% CI 1.33–24.33) greater risk of IOP rise in the DEX implant group [Table 4].
Table 3.
Time, magnitude, and dosage of IOP among steroid responders
| Variables | TA group SR n=41 eyes n (%) | DEX group SR n=24 eyes n (%) | P P |
|---|---|---|---|
| Time of IOP rise | |||
| At 3 months At 6 months At 1 year At 2 years |
19 (46.3) 19 (46.3) 2 (4.9) 1 (2.4) |
15 (62.5) 5 (20.8) 2 (8.3) 2 (8.3) |
0.2081 0.0397 0.5759 0.2744 |
| The magnitude of IOP rise | |||
| 6–15 mm Hg (Moderate responders) >15 mm Hg (Severe Responders) |
27 (65.9) 14 (34.2) |
22 (91.7) 2 (8.3) |
0.0197
0.02 |
| Dosage | |||
| 0.7mg 2 mg 4 mg |
- 34 (16.9) 7 (11.9) |
24 (19.7) - - |
NA |
% Column percentage; P - Proportion test; Boldface indicates statistical significance (P<0.05); NA - Not Applicable (fixed DEX dose: 0.7 mg)
Table 4.
Cox proportional hazardous analysis
| Parameters | TA group SR n=41 eyes HR (95% CI) | P | DEX group SR n=24 eyes HR (95% CI) | P |
|---|---|---|---|---|
| Age | 0.99 (0.95-1.03) | 0.637 | 0.95 (0.91-1.01) | 0.06 |
| Gender - Female | 0.58 (0.29-1.13) | 0.120 | 0.48 (0.02-7.8) | 0.556 |
| Asthma | NC | NC | 0.41 (0.04-10.63) | 0.989 |
| Cardiac | 0.64 (0.23-1.8) | 0.406 | 0.99 (0.30-3.23) | 0.206 |
| Diabetes | 1.22 (0.56-2.66) | 0.632 | 2.17 (0.65-7.23) | 0.373 |
| Hyperlipidemia | 0.97 (0.43-2.18) | 0.959 | 0.55 (0.15-2.01) | 0.894 |
| Hypertension | 0.54 (0.28-1.03) | 0.065 | 0.93 (0.34-2.55) | 0.461 |
| Nonocular surgery | 0.85 (0.26-2.79) | 0.801 | 0.40 (0.03-4.46) | 0.060 |
| Renal disease | 1.30 (0.37-4.46) | 0.674 | 3.42 (0.95-12.39) | 0.763 |
| Thyroid | 0.98 (0.22-4.43) | 0.981 | 0.72 (0.08-6.01) | 0.861 |
| Others | 2.78 (0.94-8.17) | 0.063 | 5.71 (1.33-24.33) | 0.018 |
HR: Hazard Ratio; CI: Confidence Interval; Boldface indicates statistical significance (P<0.05); NC: Not Computed (single case only)
From the Kaplan–Meier survival estimate graph, it was observed that the SR due to DEX implant was 50% at 3 months, compared to 59% in the TA group. The proportion of patients who responded to the steroids was nearly identical at the 1-year mark: 91.7% for DEX implant and 97.6% for IVTA. Therefore, the differences between the two groups were not statistically significant (P value = 0.74) [Fig. 1].
Figure 1.
Kaplan–Meier survival estimate graph showing the steroid response for DEX implant and IVTA groups
Both univariate and multivariable logistic regression analyses were conducted using SR and NR as the outcome variables, and the results are given in Supplementary Table S1. In the multivariable model for the IVTA group, the patients with baseline IOP below 17 mmHg showed a significantly higher chance of SR as compared to those patients with baseline IOP ranging from 17 to 21 mmHg (OR = 3.78, P = 0.023). No other predictors were found to be significantly associated with the outcome variable in both the implant groups. Nearly 66% were moderate responders of steroids in TA group, whereas it is 92% in DEX group (P = 0.0197) and it is vice versa for the severe responders (34.2% vs. 8.3%, P = 0.02).
Supplementary Table S1.
Baseline characteristics of patients/eyes with steroid treatment
| Parameters | TA group n=260 patients n (%) | DEX group n=122 patients n (%) | P |
|---|---|---|---|
| Number of injections (patients) | |||
| 1 2 3 |
170 (65.4) 88 (33.4) 2 (0.7) |
87 (71.3) 33 (27.1) 2 (1.64) |
0.249P 0.183P 0.436P |
| Injections (Months) | |||
| Time interval between first and last injections Mean±SD (Min-Max) |
4.32±4.57 (11 days – 40 months) |
4.93±3.98 (1 month -24 months) |
0.0036 R |
| Age (in years) | |||
| Mean±SD Range |
59.02±8.21 (37-86) |
57.2±10.22 (27-82) |
0.06T |
| Gender | |||
| Male Female |
146 (56.2) 114 (43.8) |
87 (71.3) 35 (28.7) |
0.005
P
0.0046 P |
| Eye (s) | |||
| Right eye Left eye |
134 (51.5) 126 (48.5) |
68 (55.7) 54 (44.3) |
0.443C |
| Etiology | |||
| BRVO CRVO DME |
91 (35) 60 (23.1) 109 (41.9) |
52 (42.6) 29 (23.7) 41 (33.6) |
0.1512P 0.8812P 0.1207P |
| Need for AGM at final visit | |||
| No Yes |
240 (92.3) 20 (7.7) |
105 (86.1) 17 (13.9) |
0.06C |
| Systemic illness*P | |||
| Asthma Cardiac Diabetes Hyperlipidemia Hypertension Nonocular surgery Renal Thyroid Others |
12 (2.2) 41 (7.42) 193 (34.9) 65 (11.77) 167 (30.25) 29 (5.25) 14 (2.53) 14 (2.53) 17 (3.1) |
4 (1.53) 22 (8.5) 85 (32.69) 33 (12.69) 84 (32.3) 6 (2.3) 12 (4.6) 6 (2.3) 8 (3.1) |
0.543 0.607 0.524 0.708 0.554 0.053 0.116 0.844 0.074 |
| Baseline IOP | |||
| Mean±SD (Min-Max) |
16.62±2.9 (8-21) |
16.63±2.78 (10-21) |
0.933R |
| Refractive error status | |||
| No Yes |
141 (54.2) 119 (45.7) |
65 (53.3) 57 (46.7) |
0.862C |
| Steroid responsiveness | |||
| Steroid Non-Responder (NR) Steroid Responder (SR) |
219 (84.2) 41 (15.8) |
98 (80.3) 24 (19.7) |
0.344C |
% Column Percentage; *Some patients had more than one systemic illness; BRVO: Branch Retinal Vein Occlusion; CRVO: Central Retinal Vein Occlusion; DME: Diabetic Macular Edema; NR - Increase in the IOP at final visit is less than 5 mmHg; SR - More than 5 mmHg increase in the IOP at final visit; R - Wilcoxon rank sum test; P - Proportion Test; C - Chi-Square test; Bolded P-value is significant (P<0.05)
Discussion
The present study compared the incidence, risk factors, and magnitude of IOP rise following intravitreal TA and DEX intravitreal implant in patients with retinal diseases. In our study, the mean age of patients who received DEX intravitreal implant (57.2 ± 10.22 years) was marginally lower as compared to those who received IVTA (59.02 ± 8.21 years). The gender ratio was somewhat higher in the DEX group (male, 71.3%) as compared to the IVTA group (male, 56.2%). This is in agreement with the previous observations that males readily get accessed to health care due to cultural factors in our society.[13]
Earlier studies reported several risk factors for SI-OHT following IVTA such as young age,[3,14] multiple IVTA injection,[15,16] pre-existing glaucoma,[15,17] male gender,[15] higher baseline IOP, and increased TA dosage. Our present study revealed that age, number of injections, and gender were not found to be associated with the incidence of SI-OHT. This is in agreement with the previous observations for age.[15,18,19] The present study included patients who has received either IVTA/DEX implant in one eye. Around 65% of the patients received only one injection within the study duration [Table 1].
Considering the aging population of the study cohort of the present study, diabetes is the common systemic illness and DME was higher among the TA group (41.9%), whereas BRVO was higher in DEX group (42.6%). This indicates that along with DME being the major indicator for the intravitreal steroid injections, BRVO is becoming a more prevalent conditions for the use of intravitreal steroids. This could be due to the improved clinical efficacy of DEX implant for macular edema following BRVO.
The incidence of SI-OHT in both groups was found to be 15.8% (TA group) and 19.7% (DEX intravitreal insert group) at some point during the follow-up of 4.3 ± 4.5 months and 4.9 ± 3.98 months, respectively. When we analyzed the different timeline for IOP rise, it is found that 46% showed elevated IOP in IVTA group at 3 months duration, whereas in DEX implant group, it is found to be 62.5%. Similarly, the incidence of SI-OHT was 46% in IVTA group and in DEX implant group; it dropped from 62% to 21% at 6 months duration. The incidence of elevated IOP following DEX implant is comparable with the previous study;[11] however, the observed incidence of the same with IVTA was higher (46%) in the present study as compared to the previous study (27%). This could be due to the difference in the dose of TA used in our cohort of patients. The majority of the patients received 2 mg TA (77.3%) in our cohort, whereas no such information is available in Badrinayanan et al. (2022).[11]
The dosage administered for IVTA injections is variable between 1 and 25 mg.[17] It is documented that lesser the dose (1 mg), lesser the incidence of elevated IOP as compared to 4 mg dose. In our cohort, a majority of our patients received 2 mg (77.3%) and the incidence was 16.9%, and in those who had received 4 mg TA (22.7%), it was 11.9%. Although the major proportion of the patients among IVTA group received 2 mg dose, no dose-dependent IOP rise was noted. Higher incidence of SI-OHT was found with 2 mg as compared to 4 mg, which is in contrary to the previous studies.[18] This could be due to variations in the number of injections required to treat the existing conditions.
In IVTA-SR group, there was a significant rise in IOP (13.51 ± 10.52) as compared to DEX group (9.5 ± 3.91). This is in agreement with the previous studies.[12,20,21] Interestingly, this difference could be due to IVTA being administered as a suspension form wherein DEX is an insert. IVTA suspension releases the drug immediately and thereby causes early IOP rise by volume expansion or physical clogging of the TM.[21,22]
The onset and duration of OHT after intravitreal administration of corticosteroids vary according to the molecule and dose. In the present study, the magnitude of IOP rise in IVTA group was at 15 months, whereas it took 2 years for the DEX implant group. This is in agreement with the previous findings that with 1 mg IVTA, the median number of days since first injection to IOP elevation greater than 10 mmHg from baseline was 34 d (21–598 d) and 53.5 d (26–135 d) for the patients treated with 4 mg IVTA.[18] The time course of OHT for dexamethasone implantation was found to be 1.5–2.5 months interval.[22] Likewise, in our present study, we have documented longer follow-up in DEX implant up to 2 years.
When investigating the association between systemic illness and steroid responsiveness, renal disease was found to be associated as a risk for SR, in DEX group (P = 0.048). Further studies are warranted to establish a link between the associations of steroid responsiveness in patients with previous history of renal disease along with the plasma concentration of steroids.
Conclusion
To conclude, the present study observed the significantly higher incidence of SI-OHT with IVTA group as compared to DEX group at 6 months follow-up (P = 0.04). As the time progresses, the incidence dropped to 2.4% in IVTA as compared to 8.3% at 2 years. Age and gender were not associated with the risk of SI-OHT. Diabetes was the common systemic illness for SR in both the groups. Renal disease showed a significant association with the risk of SI-OHT in patients who received DEX intravitreal implant.
The limitations of the present study include the retrospective nature, lack of structural and functional information related to optic nerve health in individuals experiencing elevated IOP, poor follow-up, and inability to assess the progression of glaucomatous optic neuropathy in patients receiving intravitreal steroids. Future studies with longer follow-up and well-designed large prospective study are required to establish a causal link between the incidences of SI-OHT with long-term steroids which will help customize the dose toward personalized medicine.
Conflicts of interest
There are no conflicts of interest.
Acknowledgement
The authors acknowledge the study participants for their kind co-operation in this study.
Funding Statement
Nil.
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