Ellipsoid Zone Loss as an Outcome Measure in MAK-Associated Retinitis Pigmentosa

Purpose: To analyze the clinical characteristics of MAK-associated retinitis pigmentosa (MAK-RP) to better outline the natural history and outcome measurements of disease. Design Retrospective case series. Methods: 18 individuals (7 female) from 16 families with pathogenic mutations in the MAK gene and a diagnosis of retinitis pigmentosa were selected from the records of the Division of Ophthalmic Genetics at Columbia University Irving Medical Center. Comprehensive retinal examination with imaging was completed for each patient; including fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT). Full-field electroretinogram (ffERG) was completed in 12 patients, visual field testing was completed in 5 patients. Progression rates of the ellipsoid zone (EZ), outer nuclear layer (ONL) were measured and compared among eyes. Results: All patients were homozygous for MAK-RP (Alu insertion at exon 9). Age at initial visit ranged from 20 years to 83 years. Median BCVA was 20/25 in the right and left eye. 33% of patients developed cystoid macular edema. Mean EZ horizontal width at first visit was 3781 µm. EZ horizontal width declined 209.78 µm/year (95% CI: 181.37-238.18, P < .001), foveal outer nuclear layer (ONL) thickness declined 1.24 µm/year (95% CI: 0.51-1.97, P = .001) accounting for age and within-subject variability. FAF imaging reveals that patients initially develop an irregular hyperautofluorescent ring, indicating more pronounced photoreceptor loss in the nasal and inferior regions. By the fifth decade of life, this ring transitions into a well-defined ellipsoid surrounding the macula. In some cases, foveal involvement may occur by the seventh decade. ffERG showed that ten patients (83%) retained attenuated photopic responses, while 6 patients (55%) exhibited detectable rod responses. Conclusions: Patients with MAK-RP maintain functional central vision and have a favorable prognosis. Therefore, alternative measures are necessary to track disease progression. On FAF, we observed that many MAK-RP patients avoid macular changes until the fifth decade of life. On OCT, our study identifies statistically significant reductions in horizontal ellipsoid zone (EZ) width and outer nuclear layer (ONL) thickness within our patient cohort.