Immediate Postoperative Alignment Measurements as a Predictor of Alignment Stability in Fixed Suture Strabismus Surgery.

PURPOSE: To evaluate the use of immediate postoperative alignment measurements as a predictor of future alignment stability in fixed suture strabismus surgery. METHODS: Forty-seven patients were prospectively evaluated after undergoing horizontal or vertical rectus muscle surgery using a fixed suture technique. Alignment measurements were taken approximately 1 hour, 1 to 3 weeks, and 2 to 3 months postoperatively. A Spearman correlation coefficient was used to compare measurements from the immediate postoperative period to the 2- to 3-month postoperative period. Patients with dissociated strabismus, only oblique muscle surgery, or poor vision in one or both eyes precluding precise alternate cover test were excluded. RESULTS: Mean age of all patients was 46.7 years (range: 12 to 86 years). Twenty-two patients underwent surgery for exotropia: 19 for esotropia and 6 for hypertropia. Mean alignment for all surgeries was 2 prism diopters (PD) undercorrection in the immediate postoperative period, which was similar to the mean of 4.6 PD undercorrection at 2 to 3 months postoperatively. However, the Spearman correlation between the immediate postoperative and 2- to 3-month postoperative measurements was 0.18 for all surgeries, 0.03 for exotropia, 0.56 for esotropia, and 0.40 for hypertropia. The overall success rate, defined as 8 PD or less of horizontal deviation and 4 PD or less of vertical deviation, was 77% at 2 to 3 months postoperatively. CONCLUSIONS: The relationship between immediate postoperative alignment and future alignment stability in fixed suture strabismus surgery has not been previously defined. The current study demonstrated that although the surgical success rate was reasonably good, poor correlation occurred between the alignment immediately postoperatively and 2 to 3 months postoperatively. [J Pediatr Ophthalmol Strabismus. 2018;55(4):240-244.].

A pilot randomized clinical trial of intermittent occlusion therapy liquid crystal glasses versus traditional patching for treatment of moderate unilateral amblyopia.

PURPOSE: To compare the effectiveness of intermittent occlusion therapy (IO therapy) using liquid crystal glasses and continuous occlusion therapy using traditional adhesive patches for treating amblyopia. METHODS: Children 3-8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled in this randomized controlled trial. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn any optimal refractive correction for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO therapy group with liquid crystal glasses (Amblyz), set at 30-second opaque/transparent intervals (occluded 50% of wear time), and a 2-hour continuous patching group (occluded 100% of wear time). For each patient, visual acuity was measured using ATS-HOTV before and after 12 weeks of treatment. RESULTS: Data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15 ± 0.12 logMAR (95% CI, 0.09-0.15) in the IO therapy group (n = 19) and 0.15 ± 0.11 logMAR (95% CI, 0.1-0.15) in the patching group (n = 15). In both groups improvement was significant, but the difference between groups was not (P = 0.73). No adverse effects were reported. CONCLUSIONS: In this pilot study, IO therapy with liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3-8 years of age with moderate amblyopia.

Chromatic pupillometry in patients with retinitis pigmentosa.

OBJECTIVE: To evaluate the chromatic pupillary response as a means of assessing outer and inner retinal function in patients with retinitis pigmentosa (RP). DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: Thirty-two patients with RP and visual loss and 43 normal subjects. METHODS: Patients were tested with a chromatic pupillometer using red and blue lights (1, 10, and 100 cd/m(2)), and their pupil responses were compared with those from 43 normal subjects (reported previously). Visual field and electroretinography (ERG) results were examined and compared with the pupil responses. MAIN OUTCOME MEASURES: The percent pupil contraction of the transient response to a low-intensity (1 cd/m(2)) blue light and high-intensity (100 cd/m(2)) red light and the sustained response to a high-intensity blue light was calculated for 1 eye of each subject. RESULTS: The pupil responses to red and blue light at all intensities were recordable in all patients except 1, whose pupil responded only to bright blue light. There was a significant difference of the pupil response between patients with RP and normal subjects in testing conditions that emphasized rod (1 cd/m(2) blue light) or cone (100 cd/m(2) red light) contribution (P<0.001). Patients with a non-recordable scotopic ERG showed significantly reduced pupil responses (P<0.001) to low-intensity blue light (1 cd/m(2)). Patients with a non-recordable or abnormal photopic ERG showed significantly reduced pupil responses (P<0.05) to high-intensity red light (100 cd/m(2)). Patients with a nonrecordable ERG had the most visual field loss and reduced pupil responses. Unexpectedly, patients with RP showed a slower re-dilation of the pupil after termination of bright blue light compared with red light, a pattern not observed in normal subjects. CONCLUSIONS: Pupil responses to red and blue light stimuli weighted to favor cone or rod input are significantly reduced in patients with RP but are still recordable in patients having a non-recordable ERG. In addition, outer photoreceptor disease appears to unmask a post-illumination pupillary constriction to bright blue light, most likely mediated by intrinsic activation of melanopsin ganglion cells. Chromatic pupillometry provides a novel, noninvasive method for following retinal functional status, particularly in patients with severe RP and non-recordable ERG.

Chromatic pupil responses: preferential activation of the melanopsin-mediated versus outer photoreceptor-mediated pupil light reflex.

OBJECTIVE: To weight the rod-, cone-, and melanopsin-mediated activation of the retinal ganglion cells, which drive the pupil light reflex by varying the light stimulus wavelength, intensity, and duration. DESIGN: Experimental study. PARTICIPANTS: Forty-three subjects with normal eyes and 3 patients with neuroretinal visual loss. METHODS: A novel stimulus paradigm was developed using either a long wavelength (red) or short wavelength (blue) light given as a continuous Ganzfeld stimulus with stepwise increases over a 2 log-unit range. The pupillary movement before, during, and after the light stimulus was recorded in real time with an infrared illuminated video camera. MAIN OUTCOME MEASURES: The percent pupil contraction of the transient and sustained pupil response to a low- (1 cd/m(2)), medium- (10 cd/m(2)), and high-intensity (100 cd/m(2)) red- and blue-light stimulus was calculated for 1 eye of each subject. From the 43 normal eyes, median and 25th, 75th, 5th, and 95th percentile values were obtained for each stimulus condition. RESULTS: In normal eyes at lower intensities, blue light evoked much greater pupil responses compared with red light when matched for photopic luminance. The transient pupil contraction was generally greater than the sustained contraction, and this disparity was greatest at the lowest light intensity and least apparent with bright (100 cd/m(2)) blue light. A patient with primarily rod dysfunction (nonrecordable scotopic electroretinogram) showed significantly reduced pupil responses to blue light at lower intensities. A patient with achromatopsia and an almost normal visual field showed selective reduction of the pupil response to red-light stimulation. A patient with ganglion cell dysfunction owing to anterior ischemic optic neuropathy demonstrated global loss of pupil responses to red and blue light in the affected eye. CONCLUSIONS: Pupil responses that differ as a function of light intensity and wavelength support the hypothesis that selected stimulus conditions can produce pupil responses that reflect phototransduction primarily mediated by rods, cones, or melanopsin. Use of chromatic pupil responses may be a novel way to diagnose and monitor diseases affecting either the outer or inner retina.

Sodium channels contribute to microglia/macrophage activation and function in EAE and MS.

Loss of axons is a major contributor to nonremitting deficits in the inflammatory demyelinating disease multiple sclerosis (MS). Based on biophysical studies showing that activity of axonal sodium channels can trigger axonal degeneration, recent studies have tested sodium channel-blocking drugs in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and have demonstrated a protective effect on axons. However, it is possible that, in addition to a direct effect on axons, sodium channel blockers may also interfere with inflammatory mechanisms. We therefore examined the novel hypothesis that sodium channels contribute to activation of microglia and macrophages in EAE and acute MS lesions. In this study, we demonstrate a robust increase of sodium channel Nav1.6 expression in activated microglia and macrophages in EAE and MS. We further demonstrate that treatment with the sodium channel blocker phenytoin ameliorates the inflammatory cell infiltrate in EAE by 75%. Supporting a role for sodium channels in microglial activation, we show that tetrodotoxin, a specific sodium channel blocker, reduces the phagocytic function of activated rat microglia by 40%. To further confirm a role of Nav1.6 in microglial activation, we examined the phagocytic capacity of microglia from med mice, which lack Nav1.6 channels, and show a 65% reduction in phagocytic capacity compared with microglia from wildtype mice. Our findings indicate that sodium channels are important for activation and phagocytosis of microglia and macrophages in EAE and MS and suggest that, in addition to a direct neuroprotective effect on axons, sodium channel blockade may ameliorate neuroinflammatory disorders via anti-inflammatory mechanisms.

Upregulation and colocalization of p75 and Nav1.8 in Purkinje neurons in experimental autoimmune encephalomyelitis.

Recent studies have indicated that, in addition to demyelination and axonal degeneration, a third factor, dysregulated ion channel expression, contributes to the pathophysiology of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Consistent with this suggestion, upregulated expression of sodium channel Na(v)1.8 is observed in Purkinje neurons in EAE and MS, and biophysical studies indicate that aberrant expression of Na(v)1.8 produces abnormal Purkinje cell firing which may contribute to the development of cerebellar ataxia. However, the molecular mechanisms that contribute to the upregulation of Na(v)1.8 in Purkinje cells in EAE and MS have not yet been determined. Previous studies have shown that neurotrophic factors can modulate sodium channel expression and that elevated levels of NGF are present in EAE and MS. Using immunocytochemical methods, we examined the relationship between the upregulation of Na(v)1.8 and the expression of the NGF receptors p75 and TrkA in EAE. Here we demonstrate that upregulation of Na(v)1.8 is associated with expression of p75 and low levels of TrkA in the majority of Purkinje cells in EAE. These findings, together with previous studies demonstrating a modulatory role of NGF on sodium channel expression, suggest that NGF acting via p75 contributes to the upregulation of Na(v)1.8 in Purkinje cells in EAE.