Efficacy of intravitreal dexamethasone implant in chronic central serous chorioretinopathy: A pilot study

Umesh C Behera; Miloni Shah; Anup Kelgaonkar; Jyotiranjan Sahoo; Raja Narayanan; Srinivas R Sadda

doi:10.4103/IJO.IJO_2523_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 2 | Page : 426-429

Efficacy of intravitreal dexamethasone implant in chronic central serous chorioretinopathy: A pilot study

Umesh C Behera¹, Miloni Shah¹, Anup Kelgaonkar¹, Jyotiranjan Sahoo², Raja Narayanan³, Srinivas R Sadda⁴
¹ Retina Vitreous Service, Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, Odisha, India
² Department of Community Medicine, Institute of Medical Sciences and SUM Hospital, Siksha ‘O’ Anusandhan Deemed to be University, Bhubaneswar, Odisha, India
³ Retina Vitreous Service, Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, Telangana, India
⁴ Retina Vitreous Service, Doheny Eye Institute, University of California, Los Angeles, CA, United States

Date of Submission	01-Oct-2022
Date of Acceptance	08-Dec-2022
Date of Web Publication	28-Apr-2023

Correspondence Address:
Umesh C Behera
L V Prasad Eye Institute, Bhubaneswar - 751 024, Odisha
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJO.IJO_2523_22

Abstract

In a prospective proof-of-concept study probing the role of para-inflammation in central serous chorioretinopathy (CSC) pathogenesis, eligible subjects with chronic CSC non-responsive to conventional treatment received a single dexamethasone (DEX) implant monotherapy. Six middle-aged males (mean age = 46.5 ± 10.8 years) with a mean disease duration of 4.5 ± 2.5 years, at the primary efficacy endpoint of six weeks, showed complete resolution of subretinal fluid (SRF) in four out of six eyes, significant reduction of SRF height (174 ± 86 μm to 22 ± 34 μm; P = 0.028) and central subfield thickness (347 ± 139 μm to 180 ± 47 μm; P = 0.003), indicating DEX as a promising treatment option for chronic CSC.

Keywords: Atypical, central serous chorioretinopathy, complex, corticosteroids, DEX, Ozurdex

How to cite this article:
Behera UC, Shah M, Kelgaonkar A, Sahoo J, Narayanan R, Sadda SR. Efficacy of intravitreal dexamethasone implant in chronic central serous chorioretinopathy: A pilot study. Indian J Ophthalmol Case Rep 2023;3:426-9

How to cite this URL:
Behera UC, Shah M, Kelgaonkar A, Sahoo J, Narayanan R, Sadda SR. Efficacy of intravitreal dexamethasone implant in chronic central serous chorioretinopathy: A pilot study. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 4];3:426-9. Available from: https://www.ijoreports.in/text.asp?2023/3/2/426/374949

The current understanding of central serous chorioretinopathy (CSC) pathogenesis revolves around excessive fluid loading in the choroid, possibly secondary to exogenous or endogenous corticosteroid imbalance, psychological stress, or genetic predisposition, but the exact pathomechanism is still elusive. Corticosteroids are fraught with the risk of worsening the disease and are avoided in the management of CSC. But there is mounting evidence of low-grade inflammation resultant of venous enlargement and remodeling contributing to the disease pathogenesis.^[1] To maintain tissue homeostasis in chronic disease, cells of the innate immune system mount an immune response (para inflammation)^[2] which, if sustained, may mimic classic immune responses, manifesting morphologically as persistent disease, intraretinal fluid, and cystoid changes.^[3] Upregulation of proinflammatory cytokines like interleukin (IL)-5, I-L6, IL-8, IL-10, IL-12, and tumor necrosis factor alpha (TNF-α) in serum and aqueous humor in CSC support the inflammatory hypothesis.^[4],[5] However, the recommended therapeutic approaches for chronic CSC, like photodynamic therapy (PDT), subthreshold micropulse lasers (SMPL), and oral eplerenone, do not target the inflammatory component of the disease.^[6],[7]

This pilot study investigated the effect of dexamethasone (DEX) implants in treating chronic and recurrent CSC.

Case Series

This study was approved by the institutional review board (2021-128-BHR-45) and registered with the clinical trials registry of India (CTRI/2022/01/039632). The tenets of the Declaration of Helsinki were followed.

Adults of both genders with a known history of waxing and waning CSC of more than six months with multimodal imaging evidence of chronic CSC were included in the study. The exclusion criteria were those with best-corrected visual acuity (BCVA) better than 20/40 in the study eye, macular photocoagulation for CSC within six months of enrolment, eyes with choroidal neovascularization (CNV) demonstrable on multimodal imaging, fellow eye vision of <20/200, aphakic eyes, history of glaucoma, and coexisting macular disease other than CSC contributing to vision loss.

Intravitreal injection of 0.7 mg DEX implant (Ozurdex; Allergan, Inc.) was administered as monotherapy. Patients received no additional ocular or systemic treatment during the study period. In bilateral disease, the eye that was the worst visually affected was chosen for treatment. The contralateral eye was monitored as a control.

Change in the height of SRF, change in BCVA, and complete resolution of SRF were the primary outcomes measured at 6 and 12 weeks. The secondary outcome measures were changes in subfoveal choroidal thickness, central subfield thickness, and intraocular pressure.

Statistical analysis was done using IBM SPSS Statistics version 27 (IBM Corp. USA). Repeated measures of analysis of variance (ANOVA) or Friedman test were used to determine significance. A P value less than 0.05 was considered statistically significant.

Six patients consented to participate. The average age was 46.5 ± 10.8 years; all were males, four (66.6%) had bilateral active CSC, and the mean duration of symptoms was 4.5 ± 2.5 years. Most (n = 4) were addicted to tobacco, and two had a history of corticosteroid-induced disease. All the study eyes had a clear crystalline lens at baseline. The various optical coherence tomography (OCT) features at baseline included presence of pigment epithelial detachment (PED; 66.6%; n = 4), intraretinal fluid (IRF; 50%; n = 3), large schitic cavities (16.6%; n = 1), large degenerative cysts (16.6%; n = 1), double layer sign (66.6%; n = 4), and intraretinal hyperreflective foci (100%; n = 6). None had choroidal neovascularization (CNV) demonstrable on multimodal imaging.

There was complete resolution of IRF, SRF, and cystoid spaces in four eyes at six weeks. Details of the patient demography, morphological changes in OCT, and change in vision are provided in [Supplementary Table 1][Additional file 1] and [Table 1]. Eyes with complete resolution of SRF showed a fragmented ellipsoid zone and absent interdigitation zone.

Table 1: Change in best-corrected visual acuity and optical coherence tomography parameters at 6 and 12 weeks of single intravitreal DEX injection in chronic central serous chorioretinopathy

Click here to view

Two eyes developed secondary open-angle glaucoma, which was controlled with a single topical anti-glaucoma medication. The contralateral control eyes did not exhibit resolution of SRF at any follow-up visit (P = 0.143). Five out of six eyes showed no recurrence at the time of their last follow-up (mean = 5.5 months; range = 3–8 months). No change in the lenticular clarity was observed at the last follow-up.

Discussion

Significant anatomical gains were observed in treating chronic CSC with DEX implants [Figure 1]. The continued treatment effect was observed in five out of six eyes for a mean follow-up of 5.5 months. Complete resolution of SRF in four out of six cases (66.6%) in this study at six weeks was higher than the reported outcome with half-dose PDT (21%), SMPL (36%), and oral eplerenone (23%) treatment in various studies that analyzed the treatment outcome at 6–12 weeks.^[7],[8] Half-dose PDT in the PLACE trial at 6–8 weeks led to complete SRF resolution in 51.2% of eyes.^[6] But the study included treatment-naïve eyes, and presence of IRF was an exclusion.

Figure 1: Late-stage fluorescein angiography (a) and indocyanine green angiography (b) of the right eye in a 30-year-old man with chronic and recurrent central serous chorioretinopathy (CSC) show window defects and ill-defined leakage at the macula and in the nasal retina. A coin-shaped blocked fluorescence—a legacy of laser photocoagulation done three years before for CSC—is seen in the temporal macula (arrow). A horizontal OCT line scan through the central macula (scanning axis shown as black line in b) shows shallow subretinal fluid (SRF), photoreceptor outer segment shedding, pigment epithelial detachment (PED) and enlarged outer choroidal vessels at baseline (c). A single dexamethasone implant resulted in complete resolution of SRF at six weeks (d) and flattening of PED at five months (e) postoperatively. The best-corrected visual acuity improved from 20/125 to 20/30

Click here to view

Anecdotal reports of intravitreal triamcinolone in CSC have shown equivocal results.^[9],[10] To the best of our knowledge, this is the first study that showed favourable response to DEX, even in eyes with features of chronicity like IRF, RPE aperatuture and schisis changes [Figure 2].

Figure 2: Color fundus photo (a) shows retinal pigment epithelium (RPE) atrophy and scarring (black arrow) in the right eye of a 45-year-old man with complex CSC. The corresponding autofluorescence image (b) shows the presence of gravitational tract (white arrow) and granular autofluorescence. Early (c) and late stage (d) fundus fluorescein images show window defects and ill-defined leaks (yellow dotted circle). The bright fluorescence of the RPE atrophy is suggestive of an RPE aperture. Baseline OCT (e) shows the presence of intraretinal fluid (IRF) pockets, schisis spaces (white arrow), and shallow SRF. OCT after two weeks of DEX implant (f) showed collapsing schisis spaces. Complete resolution of IRF and SRF was noted at six weeks (g). Best-corrected visual acuity improved from 20/160 to 20/60

Click here to view

Conclusion

This study provides promising evidence of the effectiveness of DEX implants as rescue therapy in chronic CSC. A favorable outcome to DEX implant may indirectly implicate inflammation (or para-inflammation) in chronic CSC pathogenesis. The key defining element of this study was the absence of any worsening of CSC with the DEX implant. A randomized controlled trial may validate the efficacy and safety of this novel treatment approach in chronic CSC.

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.

Acknowledgements

The study was conducted under the LEADER trial (which is a basket of trials with Ozurdex, supported by an unconditional grant of Ozurdex implants from Allergan).

Financial support and sponsorship

Hyderabad Eye Research Foundation (HERF), Hyderabad, India.

Conflicts of interest

There are no conflicts of interest.

References

1.	Spaide RF, Gemmy Cheung CM, Matsumoto H, Kishi S, Boon CJF, van Dijk EHC, et al. Venous overload choroidopathy: A hypothetical framework for central serous chorioretinopathy and allied disorders. Prog Retin Eye Res 2022;86:100973.
2.	Medzhitov R. Origin and physiological roles of inflammation. Nature 2008;454:428-35.
3.	Xu H, Chen M, Forrester JV. Para-inflammation in the aging retina. Prog Retin Eye Res. 2009;28:348-68.
4.	Karska-Basta I, Pociej-Marciak W, Chrząszcz M, Kubicka-Trząska A, Romanowska-Dixon B, Sanak M. Altered plasma cytokine levels in acute and chronic central serous chorioretinopathy. Acta Ophthalmol 2021;99:e222-31.
5.	Shin MC, Lim JW. Concentration of cytokines in the aqueous humor of patients with central serous chorioretinopathy. Retina 2011;31:1937-43.
6.	van Dijk EHC, Fauser S, Breukink MB, Blanco-Garavito R, Groenewoud JMM, Keunen JEE, et al. Half-dose photodynamic therapy versus high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy: The PLACE trial. Ophthalmology 2018;125:1547-55.
7.	Schwartz R, Habot-Wilner Z, Martinez MR, Nutman A, Goldenberg D, Cohen S, et al. Eplerenone for chronic central serous chorioretinopathy-a randomized controlled prospective study. Acta Ophthalmol 2017;95:e610-8.
8.	Scholz P, Altay L, Fauser S. Comparison of subthreshold micropulse laser (577 nm) treatment and half-dose photodynamic therapy in patients with chronic central serous chorioretinopathy. Eye (Lond) 2016;30:1371-7.
9.	Jonas JB, Kamppeter BA. Intravitreal triamcinolone acetonide and central serous chorioretinopathy. Br J Ophthalmol 2005;89:386-7.
10.	Patron ME, Vuong LN, Duker JS. Intravitreal triamcinolone acetonide for cystoid macular edema secondary to central serous chorioretinopathy. Retin Cases Brief Rep 2009;3:319-22.