Management of Cystoid Macular Edema in Retinitis Pigmentosa: A Systematic Review and Meta-Analysis

Abstract

Background: To date, various treatments for cystoid macular edema (CME) in retinitis pigmentosa (RP) have been reported. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of current treatments for RP-CME.

Methods: PubMed, Embase and the Cochrane library were searched from inception to August 2021. ClinicalTrials.gov, WHO ICTRP and ISRCTN were also searched for relevant studies. Only studies published in English were included. The RoB 2 tool was used to evaluate the risk of bias of randomized controlled trials (RCTs), and the MINORS scale was used to assess the methodological quality of non-RCTs. Review manager (Revman) was used to pool the data. The primary outcomes included the change of central macular thickness (CMT) and best-corrected visual acuity (BCVA) from baseline. The secondary outcomes included fluorescein angiography (FA) leakage, rebound of CME and adverse effects.

Results: Thirty-two studies were included in the current systematic review and 7 studies were used for meta-analysis. Treatments for RP-CME included oral and topical carbonic anhydrase inhibitors (CAIs), systematic and local steroids, anti-VEGF therapy, NSAIDS, grid LASER photocoagulation, subliminal micropulse LASER, vitrectomy, lutein supplement and oral minocycline. CAIs and local steroids were proved to be effective in reducing CMT. The effects of anti-VEGF reagents varied among studies. Regarding other treatments, only one study for each method fitted the inclusion criteria, so the evidence was very limited.

Conclusion: Topical CAIs, oral CAIs and local steroids are effective in treating RP-CME. However, due to the overall inferior design and small patient number of the included studies, the quality of evidence was poor. Systematic steroids, LASER, NSAIDS and vitrectomy may also be effective, nevertheless, considering the limited number of studies, no conclusion could be drawn regarding these treatments. More well-designed and conducted studies are needed in this field.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021273979, identifier CRD42021273979.

Keywords: carbonic anhydrase inhibitors; cystoid macular edema; meta-analysis; retinitis pigmentosa; steroids; systematic review.

Figure 1

Flow diagram of literature search and records screening.

Figure 2

Distribution characteristics of included studies. (A) Number of different study types; (B) Study number of different treatments.

Figure 3

Summary of risk of bias assessment for randomized controlled trials (RCTs) employing RoB 2 tool.

Figure 4

Forest plots for the meta-analysis of change of central macular thickness (CMT) (μm) from baseline after carbonic anhydrase inhibitors (CAIs) treatment. (A) Meta-analysis of different study types; (B) Subgroup analysis according to different administration methods of CAIs. [For the studies Chung et al. (28), Grover et al. (30)/Fishman and Apushkin (7), Apushkin et al. (29), and Ikeda et al. (35, 39), the change of CMT was calculated from published original individual data; For the study Genead and Fishman (34), the change of CMT was calculated from the mean/standard deviation data before and after treatment; For the study Liew et al. (36), the change of CMT was calculated from the mean/95% CI of CMT reduction in responders and non-responders; For the study Strong 2019, the change of CMT was calculated from the mean/standard deviation data which was extracted from the box plot from the original article by Photoshop software] [*The study Strong 2019 was used for analysis in (A) but not in (B) because oral and topical CAIs treatment data cannot be separated in this study. The study Grover et al. (30)/Fishman and Apushkin (7) was used for analysis in (A) but not in (B) because this study may share some same patients with the study Genead and Fishman (34)].

Figure 5

Forest plots for the meta-analysis of the responder proportion after carbonic anhydrase inhibitors (CAIs) treatment. (A) Meta-analysis of different study types; (B) Subgroup analysis according to different administration methods of CAIs. [Ikeda et al. defined the responder as CMT decreased 20% from baseline. We calculated the 11% decrease of CMT from their published original data; The responder rate of the study Grover et al. (30)/Fishman and Apushkin (7) was calculated from their published original data; Other studies reported the 11% reduction rate directly] [*the study Strong 2019 was used for analysis in (A) but not in (B) because oral and topical CAIs treatment data cannot be separated in this study. The study Grover et al. (30)/Fishman and Apushkin (7) was used for analysis in (A) but not in (B) because this study may share some same patients with the study Genead and Fishman (34)].

Figure 6

Plots for the change of central macular thickness (CMT) (μm) from baseline after steroids treatment. (A) CMT change (μm) in different study types; (B) CMT change (μm) of different administration methods of steroids. [for the studies Ozdemir et al. (27) and Sudhalkar et al. (19), the change of CMT was calculated from published original individual data; For the study Kitahata et al. (37), the change of CMT was calculated from the mean/standard deviation data before and after treatment; For the studies Karasu (10) and Mansour et al. (11), the change of CMT was reported in the article].

Figure 7

Autofluorescence and optical coherence tomography (OCT) images of a 41-year-old woman affected by macular edema after retinitis pigmentosa (RP) and treated with 1 injection of dexamethasone implant at baseline and at month 9. At baseline, BCVA (Snellen equivalent) was 20/50, and the presence of intraretinal fluid was detected by OCT. At months 3 and 6, BCVA improved, and a reduction in CRT was observed. At month 9, a gradual visual loss and an increase of intraretinal fluid were noted. An additional intravitreal dexamethasone implant was performed at month 9. At 12 months, BCVA improved to 20/32, and no fluid was detected by OCT. This figure was reproduced from Veritti et al. (14). The publisher for this copyrighted material is Mary Ann Liebert, Inc. publishers.