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Retinal sensitivity, horizontal ellipsoid width, and fundus autofluorescence areas are the most effective measures for assessing choroideremia progression.

“The NIGHT study found that changes from baseline in retinal sensitivity, central ellipsoid zone (EZ) area, and total area of fundus autofluorescence (FAF) could be more sensitive identifiers of early choroideremia (CHM) than best corrected visual acuity (BCVA) decline in natural disease progression,” Robert E. MacLaren, MB, ChB, DPhil, and colleagues wrote in the American Journal of Ophthalmology. “Using these outcomes as endpoints in future interventional clinical studies could help identify novel therapies for early CHM that could slow progression prior to the increased BCVA decline after 39.1 years, thus reducing the patient burden and economic burden of the disease.”

Dr. MacLaren and colleagues enrolled 318 adult males with CHM who averaged 47.1 years in the prospective, observational NIGHT study at 19 sites between 2015 and 2020.

All participants had active, clinically visible macular disease and BCVA better than or equal to 6/60 (20/200; 34 to 38 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in at least one eye. The eye with higher BCVA at the screening visit was considered the better eye. The researchers excluded patients with amblyopia or other diseases that could put them at risk or confound the results, as well as those who had participated in an interventional study within the past 6 months.

The study team assigned participants to one of three groups based on their baseline BCVA in the worse eye: 50 people in Cohort 1 (≥74 ETDRS letters), 208 in Cohort 2 (≥34 to <74 ETDRS letters), and 60 in Cohort 3 (<34 ETDRS letters).

The study team examined these patients for distance refraction at 4, 8, 12, 16, and 20 months from baseline and recorded changes in their BCVA. They also measured their functional and anatomical outcomes up to Month 12, including retinal sensitivity, central EZ area, and total FAF area.

In all cohorts, the mean BCVA showed little or no change over 20 months. Participants showed a mean change from baseline in BCVA score at Month 20 of +0.4 ETDRS letters in the worse eye and −1.1 ETDRS letters in the better eye. A few participants were labeled fast progressors: by worse eye, 27/318 (8.5%), and by better eye, 32/318 (10.1%). Baseline BCVA was not closely associated with fast progressor status.

Zachary A. Coates, OD, MS, talked with Physician’s Weekly (PW) about how measurements beyond BCVA can enable clinicians to better monitor CMH progression in their patients.

PW: What measures are most effective for assessing CHM progression?

Dr. Coates: This study found that retinal sensitivity, horizontal ellipsoid width, and fundus autofluorescence areas were the most effective measures for assessing CHM progression.

I didn’t find the primary findings of the NIGHT study surprising. It’s been known that high-contrast visual acuity is a poor measure of progression, especially in retinal conditions. I was slightly surprised that retinal sensitivity through microperimetry, central EZ area, and total FAF area did show changes, even during seemingly stable periods.

What is the importance of natural history data versus BVCA?

In inherited retinal disease, BCVA can often be misleading because it may remain stable even as physiological and functional changes occur. In these patients, natural history data helps develop better clinical markers to detect progression.

How do the results help clinicians effectively treat CHM?

While the NIGHT study did not explore CHM interventions, it did demonstrate the importance of close monitoring of a patient’s FAF, retinal sensitivity, and EZ. Changes in these parameters could indicate the need to set the patient up with low vision rehabilitation or vision impairment services.

What strengths or limitations are significant?

Strengths of the NIGHT study include the large number of participants for such a rare condition and the older age of participants compared to previous studies and meta-analyses. The high attrition rate was a significant limitation, especially in the moderate cohort.

What further related research is needed?

What structural signs could there be amongst the fast-progressor cohort? Are there common findings on their FAF and optical coherence tomography that could be used to predict their outcomes? Further investigation into common features between fast progressors, whether further genetic investigations or deeper analyses of retinal evaluations, would be interesting.

Is there anything else you would like to mention?

The NIGHT study highlights that clinicians should not rely purely on BCVA to monitor for progression in patients with inherited retinal disorders. Non-invasive and readily available testing strategies like FAF, optical coherence tomography, and retinal sensitivity testing through microperimetry should be utilized to better monitor these patients.