|Year : 2022 | Volume
| Issue : 3 | Page : 234-239
To study the effect of intravitreal ozurdex implant in cases of retinal vein occlusion
Shailender K Chaudhary1, Saloni Gupta1, Gangadhar Thellam1, Rupali Tyagi1, Sahil Agrawal2
1 Department of Ophthalmology, Northern Railway Central Hospital, New Delhi, India
2 Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||31-Dec-2021|
|Date of Decision||12-Apr-2022|
|Date of Acceptance||15-May-2022|
|Date of Web Publication||22-Dec-2022|
Dr. Sahil Agrawal
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi -110029
Source of Support: None, Conflict of Interest: None
Introduction: Retinal vein obstruction is one of the leading causes of severe vision impairment and blindness with treatment options mainly including laser, vascular endothelial growth factors, and steroids. This study investigates an intravitreal dexamethasone implant (ozurdex), its efficacy, and complications in patients of retinal venous occlusion. Methods: A prospective, interventional study involving 30 patients with retinal venous occlusion. Patients diagnosed with RVO who had vision loss of at least two lines on Snellen's chart and increased central macular thickness (CMT) on OCT were included in the study. All the parameters such as best-corrected visual acuity (BCVA), CMT, and intraocular pressure (IOP) were noted at baseline for the affected eye. The patients were followed up at 1 month, 2 months, and 3 months following the implant. Result: Baseline parameters were comparable between the groups. Eyes receiving the implant had a statistically significant improvement (P < 0.001) in BCVA on the Snellen chart over the 3 months. There was also a constant decrease in macular edema and the mean difference value of CMT between baseline and 1 month, 2 months, and 3months were also found to be statistically significant. Also, a comparison of IOP between two-time points was done, between baseline and 1 month, 2 months, 3 months, and the mean difference value in IOP was also found to be significant but clinically well within the normal physiological range. Conclusion: The study concluded that an intravitreal dexamethasone implant is an effective treatment for retinal venous occlusion, and it has a statistically significant and clinically meaningful effect on BCVA and CMT. However, it may be associated with a significant rise in IOP but it is well within the physiological range.
Keywords: Dexamethasone implant, intravitreal dexamethasone, intravitreal implant, ozurdex, retinal venous occlusion
|How to cite this article:|
Chaudhary SK, Gupta S, Thellam G, Tyagi R, Agrawal S. To study the effect of intravitreal ozurdex implant in cases of retinal vein occlusion. Kerala J Ophthalmol 2022;34:234-9
|How to cite this URL:|
Chaudhary SK, Gupta S, Thellam G, Tyagi R, Agrawal S. To study the effect of intravitreal ozurdex implant in cases of retinal vein occlusion. Kerala J Ophthalmol [serial online] 2022 [cited 2023 Feb 8];34:234-9. Available from: http://www.kjophthal.com/text.asp?2022/34/3/234/364721
| Introduction|| |
Retinal vein obstruction is one of the leading causes of severe vision impairment and blindness. It is the most common retinal disorder after diabetic retinopathy and age related macular degeneration (ARMD). Among retinal vein occlusion branches, the retinal vein is most common followed by central retinal vein occlusion. The prevalence of BRVO is estimated to be between 0.6% and 1.1% and that of central retinal vein occlusion (CRVO) to be between 0.1% and 0.4%.,
Various local and systemic factors play a part in the pathophysiology of retinal vein occlusion. Occlusion of the central retinal vein leads to the backup of the blood in the retinal venous system and increased resistance to venous blood flow. This increased resistance causes stagnation of the blood and ischemic damage to the retina. It has been postulated that ischaemic damage to the retina stimulates increased production of vascular endothelial growth factor (VEGF) in the vitreous cavity. Increased levels of VEGF cause capillary leakage leading to macular edema and may also stimulate neovascularization of the posterior and anterior segments.
Currently, there are no proven treatment options available, so management has the two-fold aim of managing modifiable risk factors and treating complications like macular edema and neovascularization. The most common treatment involves periodic injections into the eye of an anti-VEGF drug to reduce the new blood vessel growth and swelling. Anti-VEGF drugs include bevacizumab, ranibizumab, and aflibercept. Intravitreal steroids have also been studied and used to treat macular edema associated with retinal venous occlusion.,, They reduce inflammatory mediators through a more widespread action that blocks VEGFs, inflammatory cytokines, and prostaglandins. Currently, the response is positive but limited due to side effects.
Ozurdex (FDA approved for diabetic macular edema in November 2015) is dexamethasone eluting vitreous implant which contains 0.7 mg (700 mcg) of dexamethasone in the NOVADUR solid polymer sustained-release drug delivery system. It is released in a biphasic manner over 6 months, with higher concentrations released for the first 6 weeks, followed by lower concentrations for the following months. After this time, the implant dissolves to CO2 and H2O leaving no residue in the eye. We, therefore, studied the effect of intravitreal dexamethasone implant on best-corrected visual acuity (BCVA), central macular edema, and intraocular pressure (IOP).
| Methods|| |
The study was designed as a prospective, longitudinal, interventional analytic study. It was conducted at the department of ophthalmology of a tertiary health care institute and included a total of 30 patients. This work was carried out according to the guidelines of the institutional review board and ethical clearance was taken. Written informed consent with full disclosure was obtained from the patients before participation in the study.
Patients diagnosed with retinal vein occlusion who had vision loss of at least two lines on the Snellen chart and increased central macular thickness (CMT) on OCT were included in the study. Exclusion criteria included patients having high IOP/glaucoma, significant cataract changes, diabetic retinopathy, ARMD, and refractive error of more than 5D. At the time of enrolment in the study, a complete medical and ocular history was taken. Comprehensive ophthalmic examination, including BCVA, gonioscopy, a detailed slit-lamp examination and fundus examination with +90D lens, Optical Coherence Tomography (CIRRUS HD-OCT Model 500) to document macular edema in the form of CMT, and IOP by Non-contact Tonometer (SHIN-NIPPON NCT-200) was recorded in all patients. Fundus fluorescein angiography was used to evaluate the extent of vascular occlusion and the degree of ischemia.
On the day of the procedure, the patient's eye was dilated well and topical lignocaine 4% was instilled. A distance of 3.5 mm was marked from the limbus in the inferotemporal or inferonasal quadrant. Prefilled ozurdex implant was injected with a 22-gauge needle in an L-shaped fashion, bevel up first going parallel to the limbus for 1 mm into the sclera and then turning the needle and entering the vitreous cavity through the pars plana aiming toward the posterior pole. A click sound confirms the delivery of the implant. The needle was then withdrawn along the same path.
All the above parameters were noted at baseline for the involved eye. The patients were followed-up at 1 month, 2 months, and 3 months following the implant into the vitreous cavity, and all the parameters were recorded for the involved eye at each visit. We also examined all the eyes with the implant on the day of the procedure or a day after the procedure to rule out any acute complications like IOP spike or vitreous hemorrhage.
| Results|| |
The mean age of patients in our study was 60.93 ± 13.07 years. There were 19 males (63.3%) and 11 females (36.7%). Out of 30 patients, 40% had CRVO, 36.7% had SuperoTempoarl - Branch retinal vein occlusion, and the remaining 23.3% had InferoTemporal - Branch retinal vein occlusion. The right eye was affected in 17 (56.7%) patients, whereas the left eye in 13 (43.3%) patients.
At baseline, BCVA was <6/60 in 6 (20%) patients, 6/60 in 8 (26.7%), 6/36 in 9 (30%), 6/24 in 6 (20%), 6/18 in 1 (3.3%), and no patients had vision 6/12 or better. At 1 month, 1 (3.3%) patient improved to 6/12, 8 (26.7%) had 6/18, 13 (43.3%) had 6/24, 3 (10.0%) had 6/36, 2 (6.7%) had 6/60, and only 3 (10.0%) patients still had BCVA <6/60. At 2 months, all patients had vision 6/60 or better; 1 (3.3%) patient improved to 6/9, 4 (13.8%) had 6/12, 13 (44.8%) had 6/18, 4 (13.8%) had 6/24, 3 (10.3%) had 3/36, and remaining 4 (13.8%) patients had vision 6/60. One patient was lost to follow-up.
At 3 months, 2 (6.9%) patients now had 6/9, 2 (10.3%) had 6/12, 8 (27.6%) had 6/18, 11 (37.9%) had 6/24, 1 (3.4%) had 3/36, and remaining 4 (13.8%) patients still had vision 6/60. Thus, the eyes receiving the implant had a highly significant improvement (P < 0.001) in BCVA over 3 months.
The mean value of CMT at baseline, 1, 2, and 3 months were 411.48 m ± 83.97, 356.62 m ± 60.61, 319.86 m ± 47.11, and 295.34μ ± 46.76, respectively, with statistically significant difference (P < 0.001) [Figure 1]. A post hoc comparison of CMT between two-time points was done. Between baseline and 1st month, 2nd month, and 3rd month, mean difference value in CMT was found to be 54.862 m, 91.621 m, 116.138 m, respectively, and they were found to be significant (P < 0.001). The mean difference valued of CMT between 1 month and 2 months, 1 month and 3 months, 2 months and 3 months were 36.759 m, 61.276 m, 24.517 m, respectively, and these were also found to be statistically significant [Figure 2].
|Figure 1: Trend of central macula thickness (CMT) over a period of 3 months|
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|Figure 2: Post Hoc comparison of central macular thickness (CMT) between two time-points|
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The mean values of IOP at baseline, 1, 2, and 3 months were 15.72 mmHg ± 1.62, 18.59 mmHg ± 2.18, 18.00 mmHg ± 1.75, and 17.52 mmHg ± 1.46, respectively [Figure 3]. Post implant comparison of IOP between two time-points was done. Between baseline and 1st month, 2nd months, and 3rd months, the mean difference value in IOP was found to be − 2.862 mmHg, −2.276 mmHg, −1.793 mmHg (P < 0.001) which are significant but clinically well within the normal physiological range. The mean difference value in IOP between 1 month and 2 months is 0.586 mmHg (P = 0.384), 1 month and 3rd month is 1.069 mmHg (P = 0.037), between 2nd month and 3rd month is 0.483 mmHg (P = 0.538), which are not significant [Figure 4].
|Figure 4: Post Hoc comparison of intraocular pressure (IOP) between two time-points|
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| Discussion|| |
Macular edema is a frequent manifestation of retinal venous occlusion and is a common cause of the diminution of vision. Intravitreal administration of corticosteroids reduces capillary permeability and the formation of secondary macular edema of various etiologies. They also restrict the migration of leukocytes and inhibit the formation of VEGF factor, prostaglandins, and other pro-inflammatory cytokines. When administered directly into the vitreous body, we can achieve the appropriate concentration of the drug directly at the site of the disease, decreasing the systemic side effects, and thus the route of administration also plays an important role.
Studies have shown clinically significant improvement and increased vision after the administration of the dexamethasone implant in patients with RVO. In the present study, the status of visual acuity, CMT, IOP after 0.7 mg dexamethasone (ozurdex) implant in cases of both CRVO and BRVO were analyzed in 30 patients, and a significant improvement was observed between pre- and post-injection CMT and BCVA values (P < 0.001) in both groups.
In our study, the change in mean visual acuity from baseline to 1 month, 2 months, and 3 months were found to be statistically significant (P < 0.001). Similarly, the studies performed by Joshi L et al. and Haller JA et al. also showed significant improvement of BCVA after dexamethasone 0.7 mg (ozurdex) implant. The Geneva study results showed visual improvement in the early period after injection, its effect showed a peak at 6 weeks and lasted for a max of 3 to 4 months, after which BCVA decreased. As our study was followed-up for 3 months, further effects could not be evaluated.
The mean difference value of CMT between baseline and 1st, 2nd and 3rd month was found to be 54.862 m, 91.621 m, 116.138 m, respectively, and all the values were found to be statistically significant. Moreover, a decrease in CMT between 1 month to 2nd and from 2nd month to 3rd month were also found to be statistically significant. The studies conducted by Xioxin Li Ningli et al. also showed statistically significant change in CMT post intravitreal dexamethasone implant injection.
On assessing adverse effects of the implant, our study showed the mean difference value in IOP from baseline and monthly follow-ups were statistically significant but were within the physiological range. Also, the mean change from 1 month to 2nd and 3rd month was not significant. The study conducted by Mayer WJ et al. showed statistically significant IOP elevation post intravitreal dexamethasone 0.7 mg implant. However, the study conducted by Haller JA et al. showed that IOP peaked at day 60 (16%) but was no different from sham by day 180.
Many studies have shown clinically significant improvement and increased vision after the administration of the intravitreal dexamethasone injection in patients with RVO., The Geneva study showed the efficacy of dexamethasone implant as 1st line treatment for RVO-related macular edema and included 40 patients with non-ischemic BRVO and 31 with CRVO. It showed significant improvement in both BCVA and CMT. However, more than 50% recurrence rates were seen in both groups after 1st and 2nd injection. Similarly, Joshi et al. reported recurrence rates of 56% and 60% in patients with RVO after the first and the second Ozurdex injections, respectively.
Many studies like Chiquet et al. compared the efficacy of intravitreal dexamethasone injection and anti-VEGF therapies in patients with treatment-naive RVO-related macular edema. They concluded that anti-VEGF-administered PRN monthly and intravitreal dexamethasone injection PRN at 6-month intervals yielded comparable outcomes after 12 months follow-up. Other studies like Coscas et al. have reported good efficacy and safety profiles of repeated dexamethasone injections.
Our study shows that ozurdex implant (dexamethasone 0.7 mg) significantly improves visual acuity and CMT in patients of retinal vein occlusion (CRVO and BRVO). The study has some limitations such as a small sample size and short duration follow-up, but it was comparable to earlier studies. It may be associated with a significant rise in IOP, but this increased IOP can be medically managed. Rarely, there may be a chance of endophthalmitis which should be promptly diagnosed and managed.
Within the last decade, intravitreal pharmacotherapy has revolutionized the therapeutic options for macular edema (ME)-associated retinal vascular diseases. With both anti-VEGF agents and corticosteroids, substantial visual and morphological improvement has been achieved as compared to those that are solely treated using laser therapy in the treatment of BRVO and CRVO. Our study also shows that ozurdex is an effective and safe method for first-line management of retinal vein occlusion. Moreover, compared with anti-VEGF therapies, the burden of injections is also reduced. Safety concerns associated with the use of ozurdex include a transient increase in IOP that is usually amenable to medical management and the formation or progression of cataracts.
Thus, dexamethasone implant is assuming increasing popularity due to its good potency and dose-consistency, the prolonged duration of action, and, compared to other corticosteroids, its favorable safety profile. However, further longer duration and bigger sample size studies are required. Alternative treatment modalities such as anti-VEGF injections and laser treatment should be available for patients who do not achieve visual improvement with ozurdex and vice versa.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]