Pupil cycle time in primary closed-angle glaucoma

Pupil cycle time was measured in fellow eyes of 118 patients with closed-angle glaucoma and 70 age- and sex-matched control subjects. Results indicate that the duration of pupil cycle time was significantly prolonged in patients with closed-angle glaucoma as compared to the control group (p less than 0.001); in addition, the prevalence of absent pupillary oscillation was significantly increased in closed-angle glaucoma patients (p less than 0.001). The implications are discussed, with particular reference to the association between closed-angle glaucoma and systemic parasympathetic neuropathy.     

Anterior segment autonomic dysfunction in ocular hypertension

Autonomic nerve function in the anterior segment of the eye was assessed by measurement of the pupil cycle time in 189 patients with ocular hypertension and 70 age- and sex-matched control subjects. Parasympathetic dysfunction was significantly present in ocular hypertensive patients with narrow irido-corneal angles, though not in wide-angle subjects. The results are discussed, with particular reference to the accumulating evidence implicating autonomic dysfunction as a significant factor in the pathogenesis of the primary glaucomas.     

Pupillary autonomic denervation with increasing duration of diabetes mellitus

BACKGROUND/AIMS: The autonomic pupillary changes in type I and II diabetic patients without clinical evidence of diabetic autonomic neuropathy (DAN) were compared with age matched controls. The relation between pupillary and cardiovascular autonomic function was assessed in the diabetic patients. METHODS: A case-control study was performed with diabetics grouped according to type and duration of diabetes. Static infrared pupillography was used to compare mean dark adapted pupil size and mean percentage changes in pupil size with pilocarpine 0.1% and cocaine 4% in the diabetic and control groups. All diabetic patients underwent cardiovascular autonomic function assessment using the Valsalva ratio, the 30:15 ratio, and testing for orthostatic hypotension. RESULTS: In total, 72 type I and 69 type II diabetic patients were compared with 120 controls. Mean dark adapted pupil size was significantly smaller in diabetic groups than controls. Except for type I diabetics with disease for less than 5 years, all patient groups had significantly greater mean percentage constriction in pupil size in response to dilute pilocarpine than controls. There was no significant difference between the mean percentage dilatation in response to cocaine 4% in diabetics and controls. A high proportion of patients had normal cardiovascular autonomic function particularly when this was assessed with the Valsalva ratio. CONCLUSIONS: Denervation hypersensitivity to dilute pilocarpine is a result of damage to the pupillary parasympathetic supply of diabetic patients. This occurs before the pupillary sympathetic pathway is affected, it can be detected early in the disease, and it may be a possible explanation for the small pupil size seen in diabetic patients. Pupillary autonomic dysfunction occurs before cardiovascular autonomic changes and detection of pupil denervation hypersensitivity to dilute pilocarpine is an inexpensive way to detect early DAN.     

Sympathetic denervation hypersensitivity of the iris in ocular hypertension

Sympathetic denervation hypersensitivity of the iris was assessed in 51 patients with ocular hypertension and 36 age- and sex-matched control subjects. Significantly increased pupillary dilatation in response to topically-applied 0.5% phenylephrine hydrochloride, suggesting sympathetic denervation hypersensitivity of the iris, was present in the ocular hypertensive group (p < 0.003). The effects of autonomic nerve function on aqueous dynamics are reviewed, and the association between autonomic dysfunction and ocular hypertension is discussed.     

Anterior segment autonomic dysfunction in ocular hypertension

Autonomic nerve function in the anterior segment of the eye was assessed by measurement of the pupil cycle time in 189 patients with ocular hypertension and 70 age- and sex-matched control subjects. Parasympathetic dysfunction was significantly present in ocular hypertensive patients with narrow irido-corneal angles, though not in wide-angle subjects. The results are discussed, with particular reference to the accumulating evidence implicating autonomic dysfunction as a significant factor in the pathogenesis of the primary glaucomas.     

Systemic autonomic function in subjects with primary angle-closure glaucoma: a comparative study of symptomatic and asymptomatic disease presentation

BACKGROUND: Autonomic dysfunction is thought to be a contributory factor in primary angle-closure glaucoma (PACG) by precipitating pupil block in anatomically predisposed eyes. This study aimed to compare systemic autonomic function between subjects who had suffered a previous episode of acute angle closure (symptomatic PACG), those who had asymptomatic PACG, and age and sex-matched controls. METHODS: Tests for systemic parasympathetic function included the heart-rate response to standing (30:15 ratio), heart-rate variation during deep breathing, and the ratio of the heart rate at phases IV and II of the Valsalva manoeuvre (Valsalva ratio). For assessment of the sympathetic nervous system, blood pressure was recorded supine and then after 2 and 5 min of standing. A modified sweat test, the sympathetic skin response, was recorded on the palm and sole. RESULTS: A total of 30 subjects were examined: eight previous symptomatic PACG, eight asymptomatic PACG and 14 control subjects. The mean ages were similar, and all except one subject were Chinese. None of the subjects had evidence of systemic dysautonomia. There was no significant difference found between the groups for the 30:15 ratio, heart-rate variation during deep respiration and the Valsalva ratio. No significant orthostatic hypotension was detected in subjects with PACG. Abnormal sympathetic skin response was not more common in PACG subjects compared to control subjects. CONCLUSIONS: This study identified no systemic autonomic dysfunction in people with PACG.     

Edge-light pupil cycle time and optic nerve disease

Edge-light pupil cycle time is a quantitative measure of pupil reaction to light, dependent on the functioning of the afferent arm of the pupillary reflex arc. It has been used as an objective assessment of optic nerve function in various neuroophthalmic diseases. In this study, pupil cycle times were determined on 60 eyes of 30 normal subjects, and a mean value of 814 ms with an upper limit of normal at 935 ms was established. The average difference between the two eyes was 34 ms, and the upper limit of normal was 79 ms. Pupil cycle times were then performed on ten eyes with optic atrophy, and all ten (100%) had abnormal values. Nine patients with multiple sclerosis were tested and abnormal cycle times were found in 15 of 18 eyes (83%). Five additional patients with questionable diagnoses were tested, and all but one had abnormal pupil cycle times. A discussion of pupil reactions in optic nerve disease is presented, and the value of edge-light pupil cycle time as a quantitative measure of nerve function is assessed.     

Parasympathetic denervation hypersensitivity of the iris in ocular hypertension

Seventy-eight ocular hypertensive patients and 47 age-and sex-matched control subjects were assessed for parasympathetic denervation hypersensitivity of the iris using topical application of 2.5% methacholine chloride solution. Constriction of the pupil in response to methacholine stimulation of the sphincter pupillae was significantly greater in the ocular hypertensive patients than the control group (P less than 0.001). The implications are discussed, with particular reference to the association between autonomic neuropathy and the primary glaucomas.     

Comparing pupil function with visual function in patients with Leber's hereditary optic neuropathy.

PURPOSE: To compare pupil function with visual function in patients with Leber's hereditary optic neuropathy (LHON) and age-matched normal control subjects. METHODS: Visual function was assessed by measuring the perceptual thresholds at five central locations in the visual field using automated static perimetry. Pupil function was assessed by recording the pupil responses to a standard intensity light stimulus (size equivalent to a Goldmann V target) presented at the same five locations in the visual field. The extent of the pupil afferent defect in LHON patients was quantified by establishing the relationship between stimulus intensity and the size of the pupil response in normal subjects and then interpolating the equivalent luminance deficit in LHON patients from the size of their pupil responses. RESULTS: At all five locations tested, the pupil responses were significantly reduced in amplitude, and the perceptual thresholds were significantly raised in LHON patients compared with normal control subjects. A nonparametric analysis of perceptual and pupil responses to perithreshold stimuli showed that a stimulus that was not perceived was three times more likely to be followed by a pupil response in a LHON patient than in a normal subject (P < 0.001). A quantitative comparison showed that the visual deficits exceeded the pupil deficits by on average 7.5 dB at all tested locations. CONCLUSIONS: Although both visual and pupil function are abnormal in LHON, there appears to be relative sparing of the pupil afferent fibers.     

The pupil in dominant optic atrophy

PURPOSE. To compare visual and pupil afferent function in dominant optic atrophy (DOA). METHODS. Patients with DOA who belonged to families showing evidence of linkage to the locus on chromosome 3q28-qter were recruited from the Moorfields Genetic Register. Patients and healthy control subjects underwent visual and pupil perimetry using a modified automated perimeter (Octopus 1-2-3; Interzeag, Schlieren, Switzerland). Five stimulus locations were tested: fixation, and at 17 degrees eccentricity along the 45 degrees and 135 degrees meridians in all four quadrants. The visual deficit (difference in decibels between the patient's luminance threshold and that in age-matched healthy control subjects) was compared directly with the pupil deficit (difference in decibels between the stimulus intensity giving the patient's pupil response and that giving an equivalent pupil response in healthy control subjects) at each test location. RESULTS. Visual deficits and pupil afferent deficits were found at all five locations. The visual deficits were significantly greater than the pupil deficits at the four peripheral locations (median difference = 6.3 dB, P: < 0.001). At fixation, the difference was not significant (median difference = 2.3 dB, P: = 0.407). CONCLUSIONS. Pupil function appears less affected than visual function at four of five locations tested. This result provides evidence that the retinotectal fibers serving the pupil light reflex are less susceptible to damage from the OPA1 genetic defect than the retinogeniculate fibers serving vision.     

A pupillographical study on the presence of organochlorine pesticides in autonomic nerve disturbance

It is well known that the effect of organophosphate pesticides on the autonomic nervous system is a cholinergic reaction. However no study has been done assessing the effect of organochlorine pesticides on the autonomic nervous system. We evaluated the autonomic nerve function using open-loop pupillography in 20 patients who had exposure to the organochlorine pesticides. Significant differences were seen in pupil area (p less than .006), velocity of both constriction and dilatation (p less than .001), and dilatation time (p less than .02), when compared with 18 normal subjects. Autonomic nerve disturbances were detected in eighteen of 20 patients (90%) by evaluating the pupillary light reflex in each patient. Sympathetic nerve inhibition i.e. sympatholytic pattern, was recognized in ten of 18 patients (55%). Four patients with sympatholytic pattern had a disturbance not only in the sympathetic nerve, but also parasympathetic nerve involvement suggesting pandysautonomia. The residue blood level of the organochlorine pesticides was examined in each patient. A high frequency of the DDE was recognized (85%). It was concluded that the toxicity of the organochlorine pesticide on the autonomic nerve appear as an inhibitory effect on pupil light reflex.     

Characterization of Pupil Responses to Blue and Red Light Stimuli in Autosomal Dominant Retinitis Pigmentosa due to NR2E3 Mutation

Purpose. We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP). Methods. Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves. Results. In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02). Conclusions. Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology.     

原发性开角型青光眼患者视野缺损和瞳孔的关系

目的：测量原发性开角型青光眼患者的瞳孔对光反射,探索青光眼患者视野缺损和瞳孔的关系。方法：连续选取2014－07／2015－10于我院就诊的原发性开角型青光眼患者86例115眼和健康个体16例23眼纳入本研究,所有受试者均接受全面的眼科检查、视野检查（ Humphrey , SITA Standard 24－2）和动态瞳孔测量（ MonCV3 Metrovision ）。依据视野检查结果和青光眼分期系统,将青光眼患者分为5个亚组,即1期亚组、2期亚组、3期亚组、4期亚组和5期亚组。瞳孔对光反射相关的测量指标包括：瞳孔直径（最小和最大瞳孔直径）、收缩和开大的潜伏时间、收缩和开大的持续时间、收缩和开大的速度、收缩幅度以及瞳孔收缩比例。使用SPSS 19．0统计软件包对测量结果进行统计分析。结果：青光眼组中4期亚组和5期亚组的最小瞳孔直径与对照组差异有统计学意义（P＝0．032,P＝0．014）;各组的瞳孔收缩速度相比,差异有统计学意义（ F＝648．675, P＜0．01）,其中5期亚组的瞳孔收缩速度小于其他亚组和对照组（P＜0．05）;3期、4期和5期亚组的瞳孔收缩比例与对照组差异有统计学意义（ P＜0．05）;瞳孔收缩速度、瞳孔收缩比例和最小瞳孔直径与青光眼的视野分期相关。结论：原发性开角型青光眼患者的瞳孔瞳孔收缩能力有所下降,瞳孔收缩能力的下降与视野缺损程度相关。     

准分子激光原位角膜磨镶术对托吡卡胺角膜渗透性的影响

目的:探讨准分子激光原位角膜磨镶术(laser in situkera-tomileusis,LASIK)对托吡卡胺角膜渗透性的影响。方法:对34例(64眼)接受LASIK治疗的近视眼患者,于术前和术后1mo测量并比较10g/L托吡卡胺扩瞳后5,10,15,20min以及25min时的瞳孔大小,并记录瞳孔达到6mm大小所需时间。结果:平均中央角膜厚度由术前555.4±32.3μm下降至术后475.6±33.5μm,差异有显著意义。术后1mo10g/L托吡卡胺扩瞳后10,15,20min时的瞳孔直径明显大于术前相应时间点的瞳孔大小,而5,25min时的瞳孔大小无显著性差别。瞳孔达到6mm大小所需平均时间由术前14.66±4.28min减少至12.42±2.16min。结论:LASIK术后托吡卡胺的扩瞳作用显著加快。LASIK导致的角膜变薄增强了托吡卡胺的角膜渗透性。     

Pupil cycle time in optic nerve compression

We measured pupil cycle time before and after treatment in 11 patients with compressive optic nerve disease. Nine patients had chiasmal tumors and two had optic neuropathy of Grave's disease. Pupil cycle time before treatment was abnormal in at least one eye of all patients and in each case, pupil cycle time improved or worsened in accordance with the response to treatment of the patient's visual acuity and visual fields. This suggests that the pupil cycle time may be used as a simple objective office test for following up patients with impaired optic nerve conduction as the result of optic nerve compression. This information is similar to that gained from visual evoked response and may be used together with other objective clinical data such as disk pallor, nerve fiber loss, and relative afferent pupillary defect.     

散瞳对波前引导LASIK的影响

目的:探讨散瞳对波前引导的LASIK治疗近视的影响。方法:对216例(384眼)接受波前引导准分子激光原位角膜磨镶术(laser in situkeratomileusis,LASIK)的患者分两组,其中暗室条件下瞳孔直径<6.5mm行虹膜识别波前引导LASIK161例(291眼)为对照组;暗室条件下瞳孔直径≥6.5mm行无虹膜识别波前引导LASIK55例(93眼)为试验组,观察在暗室条件下对照组患者散瞳后瞳孔是否变形,暗室条件下试验组患者不散瞳,患者的瞳孔是否变形。对试验组瞳孔中心偏移者进行调整后再行手术,并与对照组比较。结果:两组瞳孔变形眼数比较(χ2=27.3814;P=0.000),有统计学意义。对无虹膜识别瞳孔中心有偏移的进行调整,两组比较(χ2=3.0944,P=0.0786;χ2=0.0017,P=0.9673;χ2=0.0706,P=0.7905),术后偏中心眼数、术后视力无统计学意义。结论:波前引导的LASIK在治疗近视时,散瞳易引起瞳孔变形和瞳孔中心偏移,有瞳孔中心偏移患者需进行调整,有益于提高视觉质量。     

Subretinal membranes are associated with abnormal degrees of pupil "evasion": an index of clinical macular dysfunction

AIM: To assess whether macular dysfunction caused by unilateral subretinal neovascular membranes (SRNs) is associated with pupil "evasion" (that is, increased initial rate of re-dilation following a brief light stimulus). METHODS: Comparative observational series. 20 eyes of 10 participants, all with unilateral SRNs and healthy fellow eyes. Dynamic infrared pupillography at seven stimulus intensities (duration 1100 ms, intensities over 2 log unit range). Pupil evasion ratio (PEVR; defined as the ratio of light response amplitude to amount of recovery at the mid-time point of re-dilation expressed as a percentage) was calculated for each stimulus intensity (mean of five recordings). RESULTS: Inter-eye PEVR is significantly reduced in eyes with SRN (that is, greater pupil evasion in SRN eyes: range p = 0.002 to p = 0.05 (paired t test)) and is most apparent at higher stimulus intensities. CONCLUSIONS: PEVR is a novel parameter that is analogous to the pupil escape ratio, but measured following a short rather than a sustained light stimulus. PEVR is significantly altered by macular disease. Clinically PEVR may be used to detect occult unilateral or asymmetric maculopathy in situations such as ocular media opacities like cataract, when pupil reactions are unaffected or augmented, while other tests of retinal function are diminished. PEVR represents altered neuronal firing in cones and macular ganglion cells.     

Chromatic Pupillometry Dissects Function of the Three Different Light-Sensitive Retinal Cell Populations in RPE65 Deficiency

Purpose. The aim of the study was to objectively characterize the function of rods, cones, and intrinsic photosensitive retinal ganglion cells (ipRGCs) in patients with RPE65 mutations by using two published protocols for chromatic pupillometry, and to correlate the data with the clinical phenotype. Methods. The study group comprised 11 patients with RPE65 mutations, and for control purposes, 32 healthy probands and 2 achromats. A custom-made binocular chromatic pupillometer (Bino I) connected to a ColorDome Ganzfeld stimulator was used to assess changes in pupil diameter in response to red (640 nm) and blue (462 nm) light stimuli. Light intensities, stimulus duration, and background varied depending on the protocol used. Results were compared to the clinical phenotype, that is, visual field (Goldmann perimetry), best corrected visual acuity, and full-field stimulus testing (FST). Results. No significant differences in any of the pupil response parameters were observed in intraday or intervisit variability tests. Pupil responses to rod-weighted stimulation were significantly diminished in all RPE65 patients. Pupil responses to cone-weighted stimuli differed among RPE65 patients and did not always correlate with residual visual field and cone sensitivity loss in FST. Pupil responses to ipRGC-weighted answers were slightly but significantly diminished, and the postillumination pupil response was significantly increased. Conclusions. Chromatic pupillometry represents a highly sensitive and objective test to quantify the function of rods, cones, and ipRGCs in patients with RPE65 mutations.     

Intraocular pressure responses to systemic autonomic stimulation in diabetes mellitus

Summary The acute changes in intraocular pressure during sustained handgrip contraction (2.5 minutes duration) and the Valsalva manoeuvre (15 seconds duration), both standard tests of autonomic nerve function were studied in 14 diabetic patients and 14 similar aged control subjects.During sustained handgrip contraction, diastolic blood pressure increased by 16.35 ± 1.87 mmHg in the diabetic patients and 21.36 ± 0.66 mmHg for the control group. Mean intraocular pressure decreased by 0.71 ± 0.43 mmHg in the diabetics, p < 0.05 and 0.64 ± 0.27 mmHg, p < 0.01) in the control group.There was no correlation between the blood pressure and the intraocular pressure responses in either group.On release of handgrip contraction, mean recovery intraocular pressure over 5 minutes was significantly lower than mean baseline values for the two groups; control: baseline 14.78 ± 0.49 to 14.14 ± 0.67, p < 0.001 and diabetic: 14.57 ± 0.65 to 13.86 ± 0.72, p < 0.001.During the Valsalva manoeuvre, there was a significant rise in intraocular pressure in the control (+7.85 ± 0.75mmHg, p < 0.001) and the diabetic group (+7.93 ± 1.18mmHg, p < 0.001). 5 minutes after release of intrathoracic pressure, mean recovery intraocular pressure remained significantly below baseline values for the two groups. The Valsalva ratios were in the normal range for the control group (1.21 to 2.2) while 2 diabetics had abnormal ratios.     

Influence of central depressant drugs on pupil function: an evaluation with the pupil cycle induction test

Afferent pupillary defect is an early sign of optic nerve or chiasm disease. It can be evaluated by the Pupil Cycle Induction Test (PCIT) which assesses the difficulty in setting up regular and sustained pupil oscillations. PCIT was carried out in 30 subjects with presumably normal visual function (normal visual acuity and normal fundi) and taking benzodiazepines and/or barbiturates. In 42 out of the 60 tested eyes, response to PCIT was altered. This emphasizes the necessity of a detailed drug-taking history when investigating anterior visual pathways by means of pupil function, especially when one considers the extensive use of central nervous system depressant drugs by the general population.