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Evidence for Preserved Direct Pupillary Light Response in Leber's Hereditary Optic Neuropathy 443 442 British3ournal of Ophthalmology 1995; 79: 442-446 Evidence for preserved direct pupillary light response in Leber's hereditary optic neuropathy Br J Ophthalmol: first published as 10.1136/bjo.79.5.442 on 1 May 1995. Downloaded from Masato Wakakura, Junko Yokoe Abstract analysis in LHON,I the diagnosis of this dis- Aims/Background-Pupillary light res- order remains difficult, particularly soon after ponse is usually defective in all types of its onset. There being many patients with an optic neuropathy. However, the authors onset interval for bilateral involvement, normal have observed in patients with Leber's disc appearance, absence of circumpapillary hereditary optic neuropathy (LHON) telangiectasic microangiopathy, unconfirmed relatively normal light response, with con- family history, and/or late onset may be the sequent misdiagnosis psychogenic visual reasons for this. Colour vision tests may be loss in some cases. To confirm this clinical helpful in detecting the early involvement of impression, afferent pupillary defect was LHON,2 asymptomatic carriers, and pre- assessed by measurement ofadjusted con- symptomatic eye.3 striction amplitude (CA) and escape rate In visually evoked cortical potentials, Carroll (ER) by infrared videopupillography et al4 found abnormal values in some asympto- (Iriscorder-C 2515). matic family members. Nevertheless, some Methods-Thirteen consecutive patients LHON patients have been misdiagnosed (26 eyes) with LHON (average age 27*2 initially by the authors or others5 as psycho- years) were examined; 12 had the mito- logical visual loss owing to the fact that pupil- chondrial DNA 11778 mutation and one lary light response was nearly normal. LHON the 14484 mutation. Seven of these would thus appear to be characterised by patients had a positive family history. For highly preserved pupillary light response. In comparison, the above rates were deter- this study, pupillary light response was mined in 19 patients (23 eyes) with idio- assessed in patients with LHON and the pathic optic neuritis (ON; average age results were compared with those for patients 35*1 years), 18 patients (19 eyes) with with other types of optic neuropathy and anterior ischaemic optic neuropathy controls by videopupillography. (AION; average age 58-1 years), and 25 volunteers (50 eyes) with healthy eyes (average age 39*6 years). Subjects and methods http://bjo.bmj.com/ Results-The distribution of visual acuity A review was made ofthe results ofvideopupil- was essentially the same in all optic lography of 13 consecutive subjects (26 eyes) neuropathy groups. Reduction in CA and with LHON (average age 27-2 years), 19 increase in ER were significant in patients subjects (23 eyes) with idiopathic optic neuritis with ON and AION, but not in those with (ON, average age 35'1 years), and 18 subjects LHON. Only slight afferent pupillary (19 eyes) with anterior non-arteritic ischaemic defect was evident even 2 years after the optic neuropathy (AION, average age 58 1 on September 30, 2021 by guest. Protected copyright. onset of LHON. CA in AION and ER years). Each patient group was formed by in ON were correlated statistically with lumping together the results from left and right visual acuity and Humphrey mean eyes for individual subjects. The data were threshold deviation, while CA and ER in compared with those of 25 healthy volunteers LHON were not. (50 eyes, average age 39-6 years). LHON was Conclusion-Pupillary light response in the diagnosis for 12 patients based on the mt patients with LHON obviously differs DNA mutation at position 11778. The mt from that in patients with other types of DNA mutation was noted at position 14484 in optic neuropathy. LHON appears to be the other patient. Seven patients had a positive pathophysiologically characterised by well family history of this disorder. Examination preserved afferent fibres for pupillary was performed at various stages of optic light response (probably from W cells). neuropathy. For a comparative study of three Department of Besides being of pathogenetic interest, types of optic neuropathy, initial examination Ophthalmology, Kitasato University the detection of clinical features should results (7-60 days after subjective visual loss) School ofMedicine, facilitate the diagnosis of LHON particu- were used. Direct pupillary light response was Sagamihara, Japan larly when family history provides no recorded with an infrared videopupillometer M Wakakura J Yokoe indication. (Binocular Iriscorder Model C-2515, Hama- (Bry Ophthalmol 1995; 79: 442-446) matsu Photonics Inc, Hamamatsu, Japan) Correspondence to: Masato Wakakura, MD, originally developed by Ishikawa et al.6 This Department of device consists of an infrared sensitive silicon Ophthalmology, Kitasato University School of Leber's hereditary optic neuropathy (LHON) vidicon camera, microcomputer system for Medicine, 1-15-1 Kitasato, is a maternally inherited disease characterised calculating various variables including change Sagamihara, Kanagawa 228, by bilaterally acute or subacute central visual in pupillary area, a monitor scope, and printer. Japan. loss in men. Accepted for publication young Despite the extraordinary Light emitting diodes served as the light source 9 December 1994 development of mitochondrial (mt) DNA (peak wavelength, 605 nm). Photometric Evidence for preserved direct pupillary light response in Leber's hereditary optic neuropathy 443 A instructed not to blink as much as possible and ON Light stimulus maintain their gaze on a target appearing on a secndd viewing screen inside the pupillometer. Initial I1 Br J Ophthalmol: first published as 10.1136/bjo.79.5.442 on 1 May 1995. Downloaded from I and maximal pupillary constrictions were 4 ' I measured from direct pupillary response to light of 1 second duration. Only the direct 35h pupillary response of the affected eye was evaluated. The adjusted constriction ampli- 29 H tude (CA) was expressed as a percentage and the difference in initial and maximal pupillary 23 H areas was divided by the initial area. Repetitive pulse stimuli of 250 ms duration, essentially 17 H the same in the case of continuous light (mm2)I stimulus, were used for escape rate (ER) deter- Al = Pupillary area at the moment of tihe light mination. ER, the degree of refractoriness stimulus (mm2) from light stimuli,7 was measured and the A3 = Maximal change in pupillary area caused by results are shown in Figure 1. For measure- the stimulus (mm2) ment of corrected visual acuity, Landolt rings CR = Constriction rate (%)(A3/Al) were used as the targets, viewing distance B was 5 metres, and the results were notated in 0.25 decimal acuity. Snellen fraction acuity is not ~~~~~xJ--J "-Seconds used in Japan. The Japanese visual acuity system follows the recommendation of the l1th International Congress on Ophthal- mology (1909). Visual acuity at the start of the examination was ranged from 0 01 to 1l0. 0 2 4 6 8 10 Time These were comparable with 6/600 and 6/6 in fraction acuity, respectively. Unpaired t tests were conducted for comparison of CA, ER, mean deviation, or foveal sensitivity in each group. Linear regression analysis was carried out for comparison of CA or ER with (1) visual acuity or (2) mean threshold deviation of Humphrey automated perimetry (program 30-2) examined on the same day. Escape rate (ER) ER = S33-S2/S1-S2 1 Figure Actual recordings ofpupillary light response defining adjusted const;rction http://bjo.bmj.com/ amplitude (A) and escape rate (B). Results There were no statistical differences in visual acuity between the three optic neuropathy quantification of the light stirriulus was groups when each group was divided by the 30X JO-3 lm/sterad (lumen/steracdian) (SD acuity at 0-2; the Mann-Whitney test was used. 1 0/o). Mean deviation and foveal sensitivity in The light stimulus (diameter on the pupil, Humphrey perimetry did not differ statistically on September 30, 2021 by guest. Protected copyright. 1 2 mm) was focused to the centre cAf the pupil among the three patient groups. under open loop conditions, the stiImulus field being 15 central degrees. All meaisurements were made following subject adaptantion to the CONSTRICTION AMPLITUDE (CA) dark for at least 15 minutes in a roonn with only Mean CA in LHON was 0 45 (SD 0 09). In a dim red light source. The subjects were the controls, this value was 0-48 (0 13), and essentially the same as the former (p>0 1). In the ON and AION groups, mean CA was sig- * <0.05 nificantly less compared with the controls 4NS Statistical was I **P < 0 (p<0-005). significance only lc.. marginal between CA in LHON and ON (p=0.0l). The results for CA are shown in 0.8 Figure 2. Follow up CA results for more than a) 2 years after initial examination were obtained .t 0-6 for eight eyes of four patients but no definite I- decrease was noted 3). Linear - (Fig regression I' analysis of CA versus visual acuity showed C 0.4 0 LHON to have the lowest slope (0 023), while ! AION, the highest slope (0 38). The scatter- I I gram in Figure 4 indicates CA not to be corre- Xc 02-2 lI a lated with visual acuity in LHON (r=0.05, I p=077). The linear relation was relatively o.o LHON ON AION Contr*ols high in AION (r=0-72, p<0-001), but poor in Figure 2 Comparison ofconstriction amplitude (CA) for the three optic neurropathy ON (r=0-27, p=0 09). The correlation coeffi- groups. LHON=Leber's hereditary optic neuropathy, ON=idiopathic optic neuritis, cients of CA versus visual acuity differed statis- AION=anterior non-arteritic ischaemic optic neuropathy, NS=not significanait. tically for AION and LHON (p<0 0 1), but no 444 Wakakura, Yokoe ESCAPE RATE (ER) Mean ER in LHON was 0418 (SD 0-18).
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