Aparna Raghuram

Cone phototransduction and growth of the ERG b-wave during light adaptation

The purpose of this study was to determine whether cone redepolarization accounts for the amplitude increase of the b-wave of the human electroretinogram (ERG) during light adaptation. The time course of the b-wave amplitude increase was compared to the time course of the change in the activation phase of cone phototransduction, as derived from a delayed Gaussian model applied to the leading edge of the ERG a-wave. ERG recordings were obtained from five visually normal subjects, alternately in the presence of the adapting field (adapt-on condition) and 300ms after its temporary extinction (adapt-off condition). The proportional increase in amplitude was less for R(mp3) (maximum amplitude of P3, the massed cone photoreceptor response) than for the b-wave for both adaptation conditions, and the time course of the amplitude increase for R(mp3) was faster than that for the b-wave in the adapt-off condition. The results demonstrate that time-dependent changes in the activation phase of cone phototransduction have only a minimal role in governing the increase in the amplitude of the human cone-derived ERG b-wave during light adaptation. In addition, the systematic increase in b-wave amplitude and the decrease in b-wave implicit time in the adapt-off condition indicates that the ERG response measured shortly after adapting field offset does not necessarily represent the waveform of the dark-adapted cone ERG.

Activation phase of cone phototransduction and the flicker electroretinogram in retinitis pigmentosa.

This study examined the relationship between the activation phase of cone phototransduction and the flicker electroretinogram (ERG) in 15 patients with retinitis pigmentosa (RP) and 12 age-equivalent, visually normal control subjects. Values of Rmp3 (maximum amplitude of P3, the massed cone photoreceptor response) and S (sensitivity of cone phototransduction) were derived from a delayed Gaussian model applied to the leading edge of the ERG a-wave. Fundamental amplitude and phase of the flicker ERG were derived from responses to sinusoidal flicker presented at temporal frequencies ranging from 7.8 to 100 Hz. Patients with RP who had a reduced value of Rmp3 alone had an overall reduction in flicker ERG amplitude with a normal response phase across temporal frequency. Patients with RP who had a reduced value of S, whether or not Rmp3 was reduced, had the greatest amplitude reduction at temporal frequencies above 40 Hz and phase lags across a range of temporal frequencies. At high temporal frequencies, the amplitude reduction of the flicker ERG was predicted by the product of Rmp3 and S for all of the subjects except the three patients with RP who had the lowest fundamental amplitudes. The results indicate that there is a systematic relationship between the derived parameters of the activation phase of cone phototransduction and the characteristics of the flicker ERG in patients with RP, although the phase changes in the flicker ERG were generally greater than predicted by the derived parameters alone.

Photoreceptor and postreceptor responses in congenital stationary night blindness.

PURPOSE To investigate photoreceptor and postreceptor retinal function in patients with congenital stationary night blindness (CSNB). METHODS Forty-one patients with CSNB (ages 0.19-32 years) were studied. ERG responses to a series of full-field stimuli were obtained under scotopic and photopic conditions and were used to categorize the CSNB patients as complete (cCSNB) or incomplete (iCSNB). Rod and cone photoreceptor (R(ROD), S(ROD), R(CONE), S(CONE)) and rod-driven postreceptor (V(MAX), log σ) response parameters were calculated from the a- and b-waves. Cone-driven responses to 30 Hz flicker and ON and OFF responses to a long duration (150 ms) flash were also obtained. Dark-adapted thresholds were measured. Analysis of variance was used to compare data from patients with cCSNB, patients with iCSNB, and controls. RESULTS We found significant reduction in saturated photoreceptor amplitude (R(ROD), R(CONE)) but normal photoreceptor sensitivity (S(ROD), S(CONE)) in both CSNB groups. Rod-driven postreceptor response amplitude (V(MAX)) and sensitivity (log σ) were significantly reduced in CSNB. Log σ was significantly worse in cCSNB than in iCSNB; this was the only scotopic parameter that differed between the two CSNB groups. Photopic b-wave amplitude increased monotonically with stimulus strength in CSNB patients rather than showing a normal photopic hill. The amplitude of the 30-Hz flicker response was reduced compared with controls, more so in iCSNB than in cCSNB. The mean dark-adapted threshold was significantly elevated in CSNB, more so in cCSNB than in iCSNB. CONCLUSIONS These results are evidence of normal photoreceptor function (despite the low saturated photoresponse amplitude) and anomalous postreceptor retinal circuitry.

Effect of contrast on the frequency response of synchronous period doubling.

At temporal frequencies between approximately 30 and 70 Hz, the flicker electroretinogram (ERG) of the cone system can exhibit an alternation in response amplitude from cycle to cycle that has been termed synchronous period doubling. This phenomenon has been attributed to a nonlinear feedback mechanism at an early retinal locus. The purpose of the present study was to define the effect of stimulus contrast on period doubling in order to better understand the nature of the underlying mechanism. ERGs were recorded from three visually normal subjects in response to sinusoidal flicker ranging from 20 to 100 Hz, using stimulus contrasts of 37.7, 56.5, 75.4, and 94.2%. Period doubling was quantified as: (1) the amplitude of an harmonic component of the ERG waveform that was 1.5 times the stimulus frequency, and (2) the difference between the mean trough-to-peak amplitudes on even and odd cycles of the ERG waveform. Amplitudes were converted to responsivity by dividing by stimulus contrast. By both measures, subjects showed discrete regions of period doubling that were displaced to lower temporal frequencies as stimulus contrast was increased. The temporal frequency shift of period doubling with altered stimulus contrast can be accounted for quantitatively by postulating a neural threshold for the nonlinear feedback signal that is presumed to generate synchronous period doubling.

Frequency of Visual Deficits in Children With Developmental Dyslexia

Importance Developmental dyslexia (DD) is a specific learning disability of neurobiological origin whose core cognitive deficit is widely believed to involve language (phonological) processing. Although reading is also a visual task, the potential role of vision in DD has been controversial, and little is known about the integrity of visual function in individuals with DD. Objective To assess the frequency of visual deficits (specifically vergence, accommodation, and ocular motor tracking) in children with DD compared with a control group of typically developing readers. Design, Setting, and Participants A prospective, uncontrolled observational study was conducted from May 28 to October 17, 2016, in an outpatient ophthalmology ambulatory clinic among 29 children with DD and 33 typically developing (TD) children. Main Outcomes and Measures Primary outcomes were frequencies of deficits in vergence (amplitude, fusional ranges, and facility), accommodation (amplitude, facility, and accuracy), and ocular motor tracking (Developmental Eye Movement test and Visagraph eye tracker). Results Among the children with DD (10 girls and 19 boys; mean [SD] age, 10.3 [1.2] years) and the TD group (21 girls and 12 boys; mean [SD] age, 9.4 [1.4] years), accommodation deficits were more frequent in the DD group than the TD group (16 [55%] vs 3 [9%]; difference = 46%; 95% CI, 25%-67%; P < .001). For ocular motor tracking, 18 children in the DD group (62%) had scores in the impaired range (in the Developmental Eye Movement test, Visagraph, or both) vs 5 children in the TD group (15%) (difference, 47%; 95% CI, 25%-69%; P < .001). Vergence deficits occurred in 10 children in the DD group (34%) and 5 children in the TD group (15%) (difference, 19%; 95% CI, –2.2% to 41%; P = .08). In all, 23 children in the DD group (79%) and 11 children in the TD group (33%) had deficits in 1 or more domain of visual function (difference, 46%; 95% CI, 23%-69%; P < .001). Conclusions and Relevance These findings suggest that deficits in visual function are far more prevalent in school-aged children with DD than in TD readers, but the possible cause and clinical relevance of these deficits are uncertain. Further study is needed to determine the extent to which treating these deficits can improve visual symptoms and/or reading parameters.

Receded near point of convergence and gait are associated after concussion

Objective To examine post-concussion gait among patients with and without receded near point of convergence (NPC) and uninjured controls. Design Prospective observational study. Setting Regional sport-concussion clinic. Participants Thirty-one patients presented 10.1 [95% CI=8.1, 12.1] days post-concussion (57% female, age=16.5 [15.4, 17.7]); 38 controls were tested (55% female, age=15.5 [13.6, 17.4]). Participants completed symptom, NPC, and single/dual-task gait assessments. Exclusion criteria were a current lower extremity injury or diagnosed learning disability. Intervention The effect of group (receded NPC, normal NPC, control) and task (single/dual) were evaluated via ANOVA. NPC and gait correlations were calculated. Outcome measures NPC was the patient-reported diplopia point while a fixation target moved toward the nose. Receded NPC was >5 cm from the tip of the nose. Three inertial sensors quantified gait; variables included average gait speed, cadence, and stride length. Results Nineteen concussion patients presented with receded NPC, 12 did not. Symptom severity was not significantly different between groups (27.1 [18.6, 35.6] vs. 26.3 [17.1, 35.5]). Those with receded NPC exhibited slower average gait speed (1.02 [0.93, 1.11] m/s vs. 1.19 [1.14, 1.24] m/s, p<0.001) and shorter stride lengths (1.11 [1.05, 1.18] m vs. 1.27 [1.23, 1.31] m, p=0.001) than controls. Near NPC and single-task gait speed were moderately correlated (ρ=−0.54, p= 0.002). Conclusions Adolescents with receded NPC post-concussion exhibited significant gait-related alterations compared to healthy controls; those with normal NPC did not. Vergence and gross motor system dysfunction may be interrelated following concussion and may provide useful information to post-concussion evaluations. Competing interests Dr. Meehan receives royalties from ABC-Clio publishing for the sale of his book, Kids, Sports, and Concussion: A guide for coaches and parents, and royalties from Wolters Kluwer for working as an author for UpToDate. He is under contract with ABC-Clio publishing for a future book entitled, Concussions, and with Springer International publishing for a future book entitled, Head and Neck Injuries in Young Athletes. His research is funded, in part, by a grant from the National Football League Players Association and by philanthropic support from the National Hockey League Alumni Association through the Corey C. Griffin Pro-Am Tournament. Dr. O’Brien receives royalties from Wolters Kluwer for working as an author for UpToDate. He is under contract with Springer International publishing for a book entitled, Head and Neck Injuries in Young Athletes. Drs. Howell, Shah, and Raghuram have no conflicts of interest to report.