|Year : 2022 | Volume
| Issue : 3 | Page : 299-303
Ocular hypertension and its predictor after a single Ozurdex implant: One-year follow-up in Asian Indian eyes
Tarannum Mansoori1, Swathi Shiva1, Nagalla Balakrishna2
1 Department of Glaucoma, Anand Eye Institute, Hyderabad, Telangana, India
2 Department of Statistics, Apollo Institute of Medical Sciences, Hyderabad, Telangana, India
|Date of Submission||10-Nov-2021|
|Date of Decision||29-Dec-2021|
|Date of Acceptance||14-Mar-2022|
|Date of Web Publication||02-Nov-2022|
Anand Eye Institute, Habsiguda, Hyderabad - 500 007, Telangana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
BACKGROUND: To determine the incidence and risk factors for an increase in the intraocular pressure (IOP) after a single dexamethasone intravitreal implant (Ozurdex).
MATERIALS AND METHODS: Medical records of 41 consecutive eyes who had received a single 0.7 mg Ozurdex implant for the various vitreoretinal pathology, between March 2015 and April 2016 were reviewed retrospectively. Ocular hypertension (OHT) was defined as IOP of >22 mmHg or an increase in the IOP of >6 mmHg from the baseline. Univariate regression analysis was used to measure the predictor of OHT after the implant.
RESULTS: Among the 41 eyes, who received a single Ozurdex intravitreal implant, 6/41 (14.6%) of the injected eyes had OHT, with the peak of IOP at 1 month after the injection when compared with the baseline IOP. Eight eyes (19.5%) had preexisting glaucoma or OHT, and 4/8 (50%) of them developed sustained elevation of IOP after the injection. Two eyes had transient OHT, a day after the implant, which did not require any treatment. All the eyes were managed with topical antiglaucoma medications and none required surgery to control the IOP. Preexisting OHT or glaucoma was found to be a significant risk factor for OHT after the Ozurdex injection (P < 0.0001).
CONCLUSION: Patients with preexisting OHT or glaucoma have an increased risk of OHT following the Ozurdex implant and hence needs to be informed of the possible risk. Follow-up at a regular interval is mandatory to monitor and recognize OHT early and treat it appropriately.
Keywords: Glaucoma, intraocular pressure, ocular hypertension, Ozurdex implant
|How to cite this article:|
Mansoori T, Shiva S, Balakrishna N. Ocular hypertension and its predictor after a single Ozurdex implant: One-year follow-up in Asian Indian eyes. Oman J Ophthalmol 2022;15:299-303
|How to cite this URL:|
Mansoori T, Shiva S, Balakrishna N. Ocular hypertension and its predictor after a single Ozurdex implant: One-year follow-up in Asian Indian eyes. Oman J Ophthalmol [serial online] 2022 [cited 2022 Dec 2];15:299-303. Available from: https://www.ojoonline.org/text.asp?2022/15/3/299/360416
| Introduction|| |
Ozurdex (Allergan Inc., Irvine, California, USA) is a free-floating, biodegradable, sustained-release dexamethasone implant (DEX-I), which is present in the vitreous cavity for up to 6 months after the injection. The copolymer breaks down into glycolic acid and lactic acid, which slowly undergoes hydrolysis into carbon dioxide and water. It is approved by USA Food and Drug Administration for the treatment of macular edema (ME) following branch retinal vein occlusion (RVO) or central RVO, noninfectious posterior uveitis (NIPU),, pseudophakic cystoid ME, and diabetic ME (DME).,
Ocular hypertension (OHT) and glaucoma are the most common adverse effect of Ozurdex implant. Previous studies have reported the incidence and risk factors for intraocular pressure (IOP) elevation after the intravitreal injection of DEX-I.,,,,, Increase in the IOP in approximately one-third of patients treated with DEX-I has been reported.,,, Mechanisms involved in the IOP elevation after the administration of corticosteroids are complex. OHT can occur immediately after the injection due to a sudden increase in the intraocular volume, or weeks to months later, due to a decrease in the aqueous humor outflow caused by inhibition of the degradation of extracellular matrix material within the ultrastructure of the trabecular meshwork, inhibition of the phagocytosis of trabecular meshwork cells, resulting in the accumulation of glycosaminoglycans in the outflow channels, eventually producing an increase in the IOP.,,,,
The objective of this study was to analyze the incidence of OHT after a single 0.7 mg Ozurdex implant, identify possible risk factors for the development of OHT and the time of peak increase in the IOP after the injection, given for the various vitreoretinal diseases in Asian Indian eyes.
| Materials and Methods|| |
Medical records of the consecutive patients who received a single intravitreal injection of Ozurdex 0.7 mg between March 2015 and April 2016 at our institute were reviewed. All the patients had given written informed consent for the procedure. The data collection and the study adhered to the tenets of the Declaration of Helsinki and Internal institute ethics committee approval was obtained.
The data was collected on the clinical indications for the injection, history of systemic illness, preexisting OHT or glaucoma, history of prior use of steroids (topical/periocular/systemic/intravitreal), IOP at baseline and during the follow-up visits, as measured with Goldmann applanation tonometer (GAT) and number of antiglaucoma medications, if needed. Best-corrected visual acuity, slit-lamp examination, IOP measurement with GAT, dilated fundus evaluation were performed at all the visits as per our standard clinical protocol. IOP was recorded at baseline (preinjection), 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year after the injection. Patients with age <18 years, follow-up <12 months, patients requiring multiple Ozurdex injections, history of previous intravitreal triamcinolone acetonide injection, and neovascular glaucoma were excluded.
OHT for the study was defined as a single measurement of IOP >22 mmHg or an increase in the IOP of >6 mmHg from baseline, over the follow-up period, based on the criteria established by Armaly and Becker. The fellow eye of the patient was taken as the control. The change in IOP measurements before and after injection over a follow-up period of 1 year was analyzed in the injection and the fellow noninjected eyes.
Descriptive statistics were used to determine patient characteristics, occurrence of rise in the IOP, and need for AGM. The mean change in IOP from preoperative to postoperative visits for DEX-I was analyzed using the paired t-test and analysis of variance. A P < 0.05 was considered to be statistically significant. Univariate regression analysis was used to assess the predictor of OHT after the implant.
| Results|| |
Out of 60 eyes which had received Ozurdex implant, a total of 41 eyes, met the inclusion criteria and were analyzed. The excluded patients had received bilateral injection. The indications for the treatment were: ME secondary to RVO (n = 9), DME (n = 24), pseudophakic ME (n = 4), and NIPU (n = 4) [Table 1]. The mean age was 59.4 ± 12.9 years (range, 30–86), 17 were females and 21 eyes had pseudophakia. Nine eyes (six DME and three RVO) had received intravitreal injections of anti–vascular endothelial growth factor (anti-VEGF) prior to the study period. One patient with NIPU was treated with systemic corticosteroids and three eyes had received periocular steroid injections. None of the patients had vitrectomy.
|Table 1: Baseline characteristics of the patients who received intravitreal dexamethasone implant|
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Three eyes had vitritis in the fellow eye, for which one had received periocular steroid injection and one had received oral steroid therapy. One eye had anti-VEGF injection for DME. One eye had OHT and five had preexisting glaucoma, out of which two had undergone trabeculectomy for primary angle-closure glaucoma (PACG). Four eyes were had well-controlled IOP (on AGM) at the time of inclusion in the study and showed a rise in IOP at around 1 month after the Ozurdex injection given in the other (treated) eye, although the difference was not statistically significant when compared to the baseline IOP [Table 2]. IOP >22 mmHg was seen in three eyes and none had IOP >30 mmHg. One eye had IOP of 28 mmHg, one had 26 mmHg, and one had 23 mmHg of IOP, which was controlled with the addition of AGM. Thirty eyes had pseudophakia.
|Table 2: Comparison of intraocular pressure changes from baseline to follow-up periods in Ozurdex injection eyes and fellow eyes|
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History of glaucoma or ocular hypertension in eyes who received Ozurdex
A total of eight eyes (19.5%) were on AGM at the time of enrollment in the study and the IOP was well controlled with the medication. Four eyes had glaucoma (9.76%) and four had OHT (9.76%). Two patients had primary open-angle glaucoma (POAG), two had PACG, and out of these, two eyes had undergone trabeculectomy (4.88%).
Incidence of ocular hypertension during Follow-up
Mean IOP at baseline was 13.2 ± 3.05 mmHg and at the last follow-up visit at 1 year was 14.3 ± 2.4 mmHg. There was no difference in the IOP change between injection and fellow control eyes [Table 2]. OHT of >22 mmHg or 6 mmHg increase from the baseline IOP occurred in six eyes (14.6%). Four of the patients on glaucoma monotherapy experienced sustained IOP elevation of >25 mmHg during the follow-up. None of the patients with a history of glaucoma filtration surgery had a rise in IOP. Peak rise of IOP was seen at 1 month (mean IOP of 16.52 ± 5.35 mmHg) after the injection [Table 3]. However, this increase in IOP did not differ between the fellow eye which had not received the injection, which also showed an increase in IOP at 1 month, although it did not reach statistical significance [Table 2]. Two patients had a transient IOP elevation of 22 mmHg on the 1st day after injection and did not require any treatment. Three patients had IOP elevation of >25 mmHg and one had IOP of 32 mmHg at 1 month after the injection. All these patients were started on AGM and the IOP was controlled with additional AGM and none of them showed optic disc or visual field progression during subsequent follow-up. None of the patients required any intervention (laser or surgery) for the IOP control. However, there was an increase in the number of AGM medications used at 1-month follow-up period in patients with OHT and preexisting glaucoma.
|Table 3: Comparison of intraocular pressure in the eyes receiving Ozurdex injection and fellow eyes|
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Risk factors of ocular hypertension after Ozurdex implant
The univariate analysis identified preexisting OHT and glaucoma as the risk factors for OHT after Ozurdex implant (P < 0.0001). Age, gender, uveitis, indication for the injection, and lens status were not found to be a risk factor in the analysis (All P > 0.05).
| Discussion|| |
A study evaluated the safety and efficacy of two doses of DEX-I for the treatment of noninfectious intermediate or posterior uveitis. In this 26-week trial, eyes were randomized to a single treatment with a 0.7-mg DEX-I (n = 77), 0.35-mg DEX-I (n = 76), or sham procedure (n = 76). The percentage of eyes with IOP of >25 mmHg peaked at 7.1% for the 0.7-mg DEX-I, 8.7% for the 0.35-mg DEX-I, and 4.2% for the sham (P > 0.05 at any visit).
A multicenter clinical trial of GENEVA study reported OHT (defined as IOP >25 mmHg) in 16% of 1267 patients with ME secondary to RVO, at a single dose of 0.7 mg (n = 427), 0.35 mg (n = 414), and placebo (n = 426) during 6-month follow-up. The maximum increase of IOP occurred at 2 months at both doses, which was not different from placebo-treated group at 180 days. Five patients required laser trabeculoplasty or surgery to control the IOP.
A multicenter, retrospective ZERO study reported Ozurdex induced increase in IOP of 10 mmHg in 9% of patients out of 342 patients during an 8-month follow-up period. Six patients had IOP >35 mmHg. There was no statistically significant difference between patients with or without glaucoma.
A retrospective, comparative study evaluated the effect of single intravitreal Ozurdex injection on IOP in 92 eyes with ME alone (Group 1) and 27 eyes with ME associated with glaucoma (Group 2). They reported that the DEX-I was associated with OHT (IOP >21 mmHg) in 32.6% of the eyes after the injection. In Group 1, 21.5% and in Group 2, 59.3% had OHT after the injection. Previous OHT and glaucoma were found to be a risk factor for increase in IOP after the injection.
Meyer and Schönfeld reported an increase in IOP >5 mmHg in 69% of patients and increase of >10 mmHg in 50% of patients after Ozurdex intravitreal injection. The IOP elevation was maximum at 2 months similar to other studies.,
A randomized, multicenter (MEAD) study evaluated the occurrence, management, and clinical significance of increase in IOP in 1048 patients with DME, treated with DEX-I 0.7 mg or 0.35 mg (maximum of seven injections) or placebo. In DEX-I 0.7 mg group, IOP increase of >10 mmHg from baseline occurred in 27.7% and 24.8% in patients receiving 0.35 mg and 3.7% in placebo group and the frequency did not increase with repeat implant. Only one patient (0.3%) in DEX-I group required glaucoma filtering surgery to control OHT. Mean IOP peaked at 1.5 months or 3 months after the injection and returned to the baseline level 6 months after the injection.
SAFEDOX study analyzed the incidence, risk factors, and IOP elevation (defined as IOP of at least 25 mmHg or an increase of 10 mmHg from the baseline) after Ozurdex implant in 421 eyes (361 patients). OHT was reported for 28.5% of injected eyes over a mean follow-up of 16.8 months and 31% of cases required AGM. Younger age, male gender, history of venous occlusion, uveitis, Type 1 diabetes, preexisting glaucoma treated with dual or triple therapy were significant risk factors for OHT after the injection. OHT was most frequently seen 2 months after the injection, at 1 month in 23% and 3 months in 14%. Incidence of OHT did not increase with repeat DEX-I.
Chin et al. reported OHT (defined as single IOP measurement [with Tonopen] of >30 mmHg or increase of >10 mmHg from baseline) in 26.9% (14/59) of patients who received Ozurdex. The peak IOP was seen between 1.5 and 2.5 months after the injection.
In our study, 14.6% of eyes had OHT after the Ozurdex implant, as per the predefined criteria and only one eye (2.44%) had IOP of >30 mmHg. The peak of IOP increase was seen in 1 month in both the implant and fellow eye, and all the patients were managed with topical AGM. Two patients had a transitory rise in IOP on day 1 after the injection, which was related to an increase in the intraocular volume and they did not require any treatment for IOP control. None of the patients with preexisting glaucoma or OHT showed glaucoma progression and none of the patients required systemic AGM, glaucoma surgery, or any other intervention to control IOP. At a follow-up period of 1 year after the Ozurdex implant, all the patients had controlled IOP with or without medication. There was no statistically significant change in the IOP measurements in injection eyes when compared to the fellow control eyes. Patients with OHT or preexisting glaucoma had a statistically significant increase in IOP when compared to other patients. Patients with NIPU did not show a significant increase in IOP when compared to the patients with other indications for the injection. Hence, only preexisting OHT or glaucoma was found to be a risk factor for the OHT in our study group. This should be kept in mind when planning the second injection of DEX-I as these patients are at risk of rise in IOP and hence should be followed up closely and a follow-up visit at 1 month after injection may be suggested as mandatory, especially in patients with preexisting OHT or glaucoma. An increase in IOP after corticosteroid therapy is more frequently observed in patients with POAG. Our study also found a similar incidence of OHT as in GENEVA study. Although direct comparison cannot be made due to difference in the definition of OHT in the studies. Previous studies reported IOP peak at 1.5–3 months after the implant.,,,
We found the peak IOP at 1 month after the Ozurdex implant. Hence, clinicians must be vigilant about an increase in IOP after the implant because of a variable time of the onset of IOP spike. A study determined the pharmacokinetics and pharmacodynamics of 0.7 mg Ozurdex in 34 male monkeys (Macaca fascicularis) which was detected in the retina and vitreous for a period of 6 months, with peak concentrations during the first 2 months and reaching the steady state through 6 months.
Based on this, we recommend that the IOP should be measured and monitored at postinjection day 1 and then every 2 weeks for a month and then monthly for 6 months, so that an early rise in the IOP can be detected at the earliest.
The potential limitation of this study is its retrospective nature and small sample size. However, the advantage of this study is the comparison of the Ozurdex implant eyes with the fellow control eyes, follow-up of 1 year after the injection, and it being based on everyday real-life clinical practice of Ozurdex being used for various vitreoretinal pathology.
| Conclusion|| |
Patients with a history of OHT or glaucoma are at an increased risk of IOP elevation and hence should be monitored closely after Ozurdex implant.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]