Oral and topical carbonic anhydrase inhibitors (CAIs) are prescribed as first-line therapy for patients with retinitis pigmentosa-related cystoid macular edema (RP-CME) to help boost the retinal pigment epithelial pump — previous studies show improvement for approximately 60%, with greater efficacy when CME extends to the outer nuclear layer. However, an analysis published in Retina shows almost a third of participants with outer nuclear layer fluid did not respond to oral CAIs. Investigators suggest that the study indicates Müller cells, which have ample carbonic anhydrase, may be a part of overall treatment outcome.

Data employed in the retrospective study comprised all patients with retinitis pigmentosa who presented with unilateral or bilateral CME upon visiting an academic medical center in Seoul, Korea from March 2017 to May 2021. Mean age of the sample was 44.7±17.3 years. The 59 eyes of 39 participants were grouped into sets according to retinal layers with fluid vertically, and width of involvement horizontally. Of the total, 33 eyes (55.9%) responded to CAI therapy, attaining cyst resolution or at least a 4% reduction of foveal or parafoveal volume in 1 or more quadrants.

Responding eyes more often exhibited multi-layer CME (P =.016). By the data, individuals who responded had worse baseline best-corrected visual acuity (BCVA) of 0.35±0.27, compared with nonresponders, 0.19±0.17 (P =.009). Mean BCVA tended to increase in responding eyes (P =.047), but slightly worsen in those not responding (P =.051). Patients realizing better visual acuity also displayed external limiting membrane (P =.005) and ellipsoid zone (P =.011) width gains, compared with eyes that did not achieve better VA.

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Further, most who experienced increases in BCVA after therapy were likely to have CME that vertically ranged to the outer nuclear layer, and horizontally reached the central fovea (both 91.7%). Subfoveal choroidal thickness decreased in both those responding and not responding to CAIs, but other volume and thickness data depended on whether individuals improved with therapy — eyes that responded showed significant reduction in these parameters. Investigators speculate those with multilayer, fovea-involved CME experienced functional gains if given CAIs before there was photoreceptor damage.

RP-CME may evolve from inner nuclear layer to multi-layer CME, or from the parafovea to fovea — and along with this development, photoreceptors are disrupted. Therapy for participants with prolonged CME that impacted the ellipsoid zone achieved improved structures, but not better BCVA. Accordingly, the research proposes “early treatment of multilayer CME with foveal involvement to prevent irreversible structural damage and to potentially decelerate underlying photoreceptor loss.”

Additionally, the findings illustrated by optical coherence tomography angiography (OCT-A) imaging of flow densities show no significant change in overall macular vascular density after 3 months or more of oral CAI therapy. This may indicate RP-CME is not predominantly vasculogenic, according to the analysis.

Oral CAI therapy ranged from 125 to 500 mg per day. The study was limited by a moderately small number of patients with varying therapy length, follow-up duration, and unavailable genetic information. Notably, this is the first investigation of microvasculature and visual function changes after CAI therapy for individuals with RP-CME.

Disclosure: One study author declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Yeo JH, Min CH, Yoon YH. Effect of oral carbonic anhydrase inhibitor on cystoid macular edema associated with retinitis pigmentosa: an OCT and OCT angiography studyRetina. Published online May 13, 2022. doi:10.1097/IAE.0000000000003531