Cerebral visual impairment in CDKL5 deficiency disorder: vision as an outcome measure

Abstract

Aim: To characterize the neuro-ophthalmological phenotype of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) and assess visual acuity as a reproducible, quantitative outcome measure.

Method: We retrospectively analyzed clinical data from patients with CDD. Complete neuro-ophthalmological assessments, including visual acuity, were evaluated.

Results: Of 26 patients (22 females, four males; median age 4y, interquartile range 2y 1mo-7y 10mo), cerebral visual impairment (CVI), defined as visual dysfunction in the absence of ocular or anterior visual pathway abnormalities, was diagnosed in all those over 2 years of age. Ophthalmological examinations revealed nystagmus in 10 patients and strabismus in 24 patients. Visual acuity was measured in 24 patients, by preferential looking in all and by sweep visual evoked potential in 13. Visual acuities were lower than age expectations and demonstrated improvement in the first 3 years. Adjusting for age and sex, average preferential looking visual acuity after 2 years of age was higher in patients with intact mobility than in those who were non-mobile.

Interpretation: CVI was observed in patients with CDD. Visual acuity improved over time and correlated with mobility. Visual acuity, as a quantifiable measure of visual function, should be considered as an outcome measure in pre-clinical and clinical studies for CDD. What this paper adds Cerebral visual impairment is highly prevalent in cyclin-dependent kinase-like 5 deficiency disorder (CDD). Visual acuity is a measurable quantitative outcome measure in CDD. Visual acuity in CDD correlates with gross motor ability.

Figure 1.. Binocular visual acuities in cycles per degree (cpd) by two methods.

Acuity (Y axis) is on a log2 scale and age (X axis) in a log 10 scale. Longitudinal data from an individual are connected by line segments. Patients are indicated by sex (Female= circle, male = square) and mobility (mobile= red, non-mobile = blue). A) Preferential looking (PL) acuities. Mean normal PL acuity (gray triangles) and the 95% limits of normal acuity (gray dashed lines) are based on published results. NGD (no gradient detected) indicates the patient did not detect any grating. Lack of mobility is associated with worse PL visual acuity. B) Visual Evoked Potential (sVEP) acuities. Mean normal sVEP acuity in healthy controls (gray triangles; inverted gray triangles); the gray dashed lines represent the 95% limits of normal acuity. Visual acuities by sVEP are below normal but show some improvement in early childhood. C) The relationship of preferential looking (PL) and visual evoked potential (sVEP) acuities. Results from the 13 patients who had both PL and sVEP testing are plotted; individual patients contribute 1 to 8 points. The diagonal lines have a slope of 1.0. Data would lie on the solid line if PL and sVEP acuity values were in perfect agreement. The dashed lines are 1 octave above and below the solid line.

Figure 1.. Binocular visual acuities in cycles per degree (cpd) by two methods.

Acuity (Y axis) is on a log2 scale and age (X axis) in a log 10 scale. Longitudinal data from an individual are connected by line segments. Patients are indicated by sex (Female= circle, male = square) and mobility (mobile= red, non-mobile = blue). A) Preferential looking (PL) acuities. Mean normal PL acuity (gray triangles) and the 95% limits of normal acuity (gray dashed lines) are based on published results. NGD (no gradient detected) indicates the patient did not detect any grating. Lack of mobility is associated with worse PL visual acuity. B) Visual Evoked Potential (sVEP) acuities. Mean normal sVEP acuity in healthy controls (gray triangles; inverted gray triangles); the gray dashed lines represent the 95% limits of normal acuity. Visual acuities by sVEP are below normal but show some improvement in early childhood. C) The relationship of preferential looking (PL) and visual evoked potential (sVEP) acuities. Results from the 13 patients who had both PL and sVEP testing are plotted; individual patients contribute 1 to 8 points. The diagonal lines have a slope of 1.0. Data would lie on the solid line if PL and sVEP acuity values were in perfect agreement. The dashed lines are 1 octave above and below the solid line.