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Purpose: To compare the vessel calibre measurements between optical coherence tomography angiography (OCTA) and colour fundus photography., Methods: In this retrospective comparative study, OCTA and colour fundus images of healthy eyes and eyes with optic atrophy were evaluated. The colour fundus image was registered manually using Image J software to the OCTA image of the optic disc. Two independent graders measured the vessel calibre of the widest vein and artery in each peripapillary quadrant on a 3.4 mm diameter circle centred on the optic disc in the same location on both images. The difference in vessel calibre between the two techniques was assessed., Results: A total of 312 vessels from 29 healthy eyes and 20 eyes with atrophic optic discs were included. There was a high level of agreement between graders for measurement of vessel calibre in both colour fundus (intraclass correlation coefficient=0.93, coefficient of variation=0.07) and OCTA images (intraclass correlation coefficient=0.94, coefficient of variation=0.05). The mean vessel calibre in colour fundus images (94.5±23.2 µm) and OCT images (112.2±26.1 µm) was correlated (r=0.8, p<0.001), but the difference was statistically significant (mean difference: 17.6±1.5 µm, p<0.001). This difference was evident for both arteries (mean difference: 18.2±16.3 µm, p<0.001) and veins (mean difference: 15.1±16.2 µm, p<0.001) individually, with a similar magnitude of difference for both vessel types (p=0.08). In addition, the magnitude of difference between imaging modalities was similar in atrophic and healthy discs (17.1±15.9 vs 18.4±15.2 µm, respectively, p=0.4). The difference, however, was significantly higher in vessels with a calibre of ≤94.5 compared with larger vessels (19.3±16.3 vs 15.6±14.4 µm, respectively, p=0.02)., Conclusions: Vessel calibre measurements were significantly larger in OCTA images compared with colour fundus photographs, particularly for smaller vessels. These differences may need to be accounted for when using OCTA-derived metrics., Competing Interests: Competing interests: SRS is a consultant for Optos, Genentech, and Allergan and receives research support from Optos, Genentech, Allergan and Carl Zeiss Meditec. AS receives unrestricted grant support from GenSight, Stealth Biotherapeutics and Edison., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: To evaluate longitudinal retinal ganglion cell inner plexiform layer (GC-IPL) and macular retinal nerve fibre layer (mRNFL) thickness changes in acute Leber's hereditary optic neuropathy (LHON)., Methods: Six eyes of four patients with LHON underwent SD-OCT (optical coherence tomography) at month 1, 3, 6 and 12 after visual loss. In two eyes, the examination was carried out in the presymptomatic stage. The relationship and curves for area under the receiver operator characteristic (AUROC) were generated to assess the ability of each parameter to detect ganglion cell loss., Results: Significant longitudinal thinning of GC-IPL and mRNFL was detected in LHON. GC-IPL thinning was detectable in the deviation map during the presymptomatic stage in the inner ring of the nasal sector and then it progressively extended following a centrifugal and spiral pattern. Similarly, mRNFL thinning began in the inferonasal sector and it progressively extended. No further statistically significant changes were detected after month 3. The highest level of AUROC values at 1 month were detected in the nasal sectors and inferonasal mRNFL thickness reached AUROC value=1. All the parameters were equally able to detect ganglion cell loss from month 2 to 12., Conclusions: The natural history of GC-IPL thinning follows a specific pattern of reduction, reflecting the anatomical course of papillomacular fibres. Month 6 represents the end of GC-IPL loss. GC-IPL and mRNFL thinning is detectable before onset of visual loss. These observations can help future therapeutic approaches for both LHON carriers at high risk of conversion and patients with acute early LHON., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background/aims: With the increased efficacy of current therapy for wet age-related macular degeneration (AMD), better ways to detect wet AMD are needed. This study was designed to test the ability of three-dimensional contrast threshold Amsler grid (3D-CTAG) testing to distinguish wet AMD from dry AMD., Methods: Conventional paper Amsler grid and 3D-CTAG tests were performed in 90 eyes: 63 with AMD (34 dry, 29 wet) and 27 controls. Qualitative comparisons were based upon the three-dimensional shapes of central visual field (VF) defects. Quantitative analyses considered the number and volume of the three-dimensional defects., Results: 25/34 (74%) dry AMD and 6/29 (21%) wet AMD eyes had no distortions on paper Amsler grid. Of these, 5/25 (20%) dry and 6/6 (100%) wet (p=0.03) AMD eyes exhibited central VF defects with 3D-CTAG. Wet AMD displayed stepped defects in 16/28 (57%) eyes, compared with only 2/34 (6%) of dry AMD eyes (p=0.002). All three volumetric indices of VF defects were two- to four-fold greater in wet than dry AMD (p<0.006). 3D-CTAG had 83.9% positive and 90.6% negative predictive values for wet AMD., Conclusions: 3D-CTAG has a higher likelihood of detecting central VF defects than conventional Amsler grid, especially in wet AMD. Wet AMD can be distinguished from dry AMD by qualitative and quantitative 3D-CTAG criteria. Thus, 3D-CTAG may be useful in screening for wet AMD, quantitating disease severity, and providing a quantitative outcome measure of therapy.

Objectives: Vitreoschisis is a possible pathogenic mechanism in macular diseases. Thus, the vitreoretinal interface was evaluated in monkey eyes and patients with various macular diseases in search of vitreoschisis. It is hypothesised that vitreoschisis is present in macular holes (MH) and macular pucker (MP), but not in other maculopathies., Methods: Histopathology was studied in 14 monkey eyes and a vitrectomy specimen of a patient with macular pucker. Optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) was performed in 239 eyes: 45 MH, 45 MP, 51 dry age-related macular degeneration (AMD), 53 non-proliferative diabetic retinopathy (NPDR) and 45 controls., Results: Immunohistochemistry demonstrated lamellae in the posterior vitreous cortex of 12/14 (86%) monkey eyes. With OCT/SLO, vitreoschisis was detected in 24/45 (53%) MH and 19/45 (42%) MP eyes, but in only 7/53 (13%) NPDR, 3/51 (6%) AMD and 3/45 (7%) control eyes (p<0.001 for all comparisons). Rejoining of the inner and outer walls of the split posterior vitreous cortex was visible in 16/45 (36%) MH eyes and 15/45 (33%) MP eyes. Histopathology of the MP specimen confirmed a split with rejoining in the posterior vitreous cortex., Conclusions: Vitreoschisis was detected in half of eyes with MH and MP, but much less frequently in controls, AMD and NPDR patients. These findings suggest that anomalous PVD with vitreoschisis may be pathogenic in MH and MP.

Purpose: A recently devised 3D computer-automated threshold Amsler grid test was used to identify early and distinctive defects in people with suspected glaucoma. Further, the location, shape and depth of these field defects were characterised. Finally, the visual fields were compared with those obtained by standard automated perimetry., Patients and Methods: Glaucoma suspects were defined as those having elevated intraocular pressure (>21 mm Hg) or cup-to-disc ratio of >0.5. 33 patients and 66 eyes with risk factors for glaucoma were examined. 15 patients and 23 eyes with no risk factors were tested as controls. The recently developed 3D computer-automated threshold Amsler grid test was used. The test exhibits a grid on a computer screen at a preselected greyscale and angular resolution, and allows patients to trace those areas on the grid that are missing in their visual field using a touch screen. The 5-minute test required that the patients repeatedly outline scotomas on a touch screen with varied displays of contrast while maintaining their gaze on a central fixation marker. A 3D depiction of the visual field defects was then obtained that was further characterised by the location, shape and depth of the scotomas. The exam was repeated three times per eye. The results were compared to Humphrey visual field tests (ie, achromatic standard or SITA standard 30-2 or 24-2)., Results: In this pilot study 79% of the eyes tested in the glaucoma-suspect group repeatedly demonstrated visual field loss with the 3D perimetry. The 3D depictions of visual field loss associated with these risk factors were all characteristic of or compatible with glaucoma. 71% of the eyes demonstrated arcuate defects or a nasal step. Constricted visual fields were shown in 29% of the eyes. No visual field changes were detected in the control group., Conclusions: The 3D computer-automated threshold Amsler grid test may demonstrate visual field abnormalities characteristic of glaucoma in glaucoma suspects with normal achromatic Humphrey visual field testing. This test may be used as a screening tool for the early detection of glaucoma.

We report a case of bilateral mitochondrial optic neuropathies secondary to long-term linezolid treatment, show the nature of recovery, review the findings in the literature and propose a potential mitochondrial mechanism for linezolid-induced mitochondrial optic neuropathy. This is an observational case report and literature review with presentation of the clinical course of linezolid mitochondrial optic neuropathies through clinical and psychophysical documentation. Main outcome measures included: visual acuity, funduscopical examinations and peripapillary retinal nerve fibre layer (PRNFL) optical coherence tomography (OCT). A 6-year-old boy presented with bilateral optic neuropathies secondary to 1 year of linezolid treatment for osteomyelitis of the mandible. On presentation, visual acuities were 20/400 in both eyes, with considerable optic disc oedema, hyperaemia and PRNFL swelling confirmed by OCT. 2 weeks after the discontinuation of linezolid, visual acuities returned to 20/25 in both eyes, with reduction in the optic disc oedema, hyperaemia and PRNFL swelling. 3 months after the discontinuation of linezolid treatment, visual acuities were stable at 20/20 in both eyes, with a marked decrease in PRNFL swelling confirmed by OCT, and the development of mild temporal optic disc pallor in both eyes. Doctors should be aware of impairments of vision among patients on long-term linezolid treatment and promptly discontinue treatment to prevent irreversible vision loss. The development and resolution of bilateral optic neuropathies with considerable PRNFL swelling in this patient provide insight into the more general rubric of mitochondrial optic neuropathies.

Aims: To determine if asymptomatic carriers from a previously identified large pedigree of the Leber's hereditary optic neuropathy (LHON) 11778 mtDNA mutation have colour vision deficits., Methods: As part of a comprehensive analysis of over 200 members of a large Brazilian LHON pedigree spanning seven generations, colour vision tests were obtained from 91 members. Colour vision was tested one eye at a time using the Farnsworth-Munsell 100 (FM-100) hue colour vision test. The test was administered under uniform conditions, taking into account: ambient light levels, daylight colour temperature of 6700 kelvin, and neutral uniform background. Tests were scored using the FM-100 MS-Excel computer scoring program. Defects were determined and categorised as tritan, deutan, or protan. Categorisation of each dyschromatopsia was based on review of demonstrated axis computer generated plots and age adjusted error scores which coincided with Verriest 95% confidence intervals. Only the axis with the greatest magnitude error score was used to classify the defect. 55 of the 91 test subjects were LHON mtDNA 11778 J haplotype mutation carriers, proved by mtDNA analysis. The remaining 36 subjects were age matched non-blood relatives (off pedigree), who served as controls., Results: 27 of 55 carriers (49.10%) were shown to have colour vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the carrier group were tritan defects and the remaining 14 (52%) were deutan defects. Nine of the 27 (33%) abnormals in the carrier group were identified as having bilateral defects. Six of these were deutan, and the remaining three were tritan dyschromatopsias. Only six of the 36 (16.66%) age matched controls were found to have any type of dyschromatopsia. Five (83.3%) of these were deutan defects. The remaining one was a tritan defect. The difference between the two groups using a chi(2) test with one degree of freedom was statistically significant with a p value less that 0.001., Conclusions: Until now, LHON has always been characterised by a sudden, devastating vision loss. Asymptomatic carriers, those without vision loss, were considered unaffected by the disease. It now appears that asymptomatic carriers of the LHON mutation are affected by colour vision defects and may manifest other subtle, yet chronic, changes.

Aims: To compare the ultrastructural aspects of human extraocular muscles in two types of mitochondrial disease: chronic progressive external ophthalmoplegia (CPEO) and Leber's hereditary optic neuropathy (LHON)., Methods: Muscle samples of the medial rectus obtained from surgery in a sporadic case of CPEO associated with deleted mitochondrial DNA, and post mortem in a case of 3460/ND1 LHON were processed for electron microscopy (EM). The medial rectus from an autoptic time to fixation matched control was used to exclude postmortem artefacts., Results: The CPEO specimen revealed focal areas of disruption and abnormalities of mitochondria in some muscle fibres, creating a "mosaic-like" pattern. In the LHON specimen a diffuse increase in both number and size of mitochondria (mean diameter 0.85 mum v 0.65 mum of control, p<0.0001) with swollen appearance and disorganised cristae filled all spaces of sarcoplasmic reticulum. In some areas the excessive number of mitochondria slightly distorted myofibrils., Conclusion: EM investigation of extraocular muscles in CPEO and LHON reveals marked differences. A "mosaic-like" pattern caused by a selective damage of muscle fibres was evident in CPEO, whereas a diffuse increase in mitochondria with preservation of myofibrils characterised the LHON case. These ultrastructural changes may relate to the different expression of the two diseases, resulting in ophthalmoplegia in CPEO and normal eye movements in LHON.

Background/aims: Patients taking hydroxychloroquine (HCQ) are at risk of developing classic bull's eye maculopathy. Currently, the standard Amsler grid (AG) is one of the most useful methods to identify such lesions. However, AG is a suprathreshold target and may not detect relative central scotomas. The aim of this study was to determine if the threshold Amsler grid (TAG) test, which varies light transmission through two cross polarising filters, allows increased detection of scotomas caused by HCQ toxicity., Methods: 56 rheumatological patients taking HCQ and 12 similar patients not taking HCQ were tested by AG, red Amsler grid (RAG), and TAG., Results: No scotomas were observed in patients never treated with HCQ. Among patients who had been treated with HCQ, AG revealed scotomas in two of 56 (3.64%) patients; in contrast, six (10.7%) and 37 (66.1%) scotomas were identified by RAG and TAG testing respectively. Additionally, the average area of each scotoma detected by all three methods expanded from 34.5 square degrees of central field loss on AG testing to 71 square degrees on RAG and 117 on TAG., Conclusion: By decreasing the perceived luminance of the suprathreshold AG, TAG testing provides a novel alternative to detect shallow scotomas and areas of depressed retinal activity secondary to HCQ toxicity.

Aim: To investigate the correlation between retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) size in normal white subjects by means of optical coherence tomography (OCT)., Methods: 54 eyes of 54 healthy subjects aged between 15 and 54 underwent peripapillary RNFL thickness measurement by a series of three circular scans with a 3.4 mm diameter (Stratus OCT, RNFL Thickness 3.4 acquisition protocol). ONH analysis was performed by means of six radial scans centred on the optic disc (Stratus OCT, Fast Optic Disc acquisition protocol). The mean RNFL values were correlated with the data obtained by ONH analysis., Results: The superior, nasal, and inferior quadrant RNFL thickness showed a significant correlation with the optic disc area (R = 0.3822, p = 0.0043), (R = 0.3024, p = 0.026), (R = 0.4048, p = 0.0024) and the horizontal disc diameter (R = 0.2971, p = 0.0291), (R = 0.2752, p = 0.044), (R = 0.3970, p = 0.003). The superior and inferior quadrant RNFL thickness was also positively correlated with the vertical disc diameter (R = 0.3774, p = 0.0049), (R = 0.2793, p = 0.0408). A significant correlation was observed between the 360 degrees average RNFL thickness and the optic disc area and the vertical and horizontal disc diameters of the ONH (R = 0.4985, p = 0.0001), (R = 0.4454, p = 0.0007), (R = 0.4301, p = 0.0012)., Conclusions: RNFL thickness measurements obtained by Stratus OCT increased significantly with an increase in optic disc size. It is not clear if eyes with large ONHs show a thicker RNFL as a result of an increased amount of nerve fibres or to the shorter distance between the circular scan and the optic disc edge.

Both optic nerves were obtained at autopsy from a 28-year-old man with a 2 year history of idiopathic intracranial hypertension who had undergone bilateral optic nerve sheath decompression 14 days before death. Histopathological and ultrastructural examination of the tissue revealed fibroblasts localised to the sites of fenestration. Adipose tissue was also adherent to the optic nerve pia in areas of incised dura. No patent fistula site was observed. It was concluded that filtration of cerebrospinal fluid after optic nerve sheath decompression may occur through an enclosed bleb of fibrosis rather than through an open fistula.

Transient blurring of near vision can be due to a variety of causes. We report the case of a 35-year-old man with a 10-year history of blurring of near vision that begins 30 to 45 seconds after he starts to eat and that lasts until 10 to 15 minutes after he stops eating. Magnetic resonance imaging and computed tomography of the brain and orbits did not reveal any abnormality, and stimulation of individual cranial nerves did not result in a loss of near vision. Retinoscopic refraction revealed the loss of 1.5 dioptres of accommodative power in each eye one minute after he began to eat. To the best of our knowledge such blurring of vision at near, immediately after initiating a meal, has not been previously reported. The neuroanatomy of the accommodation and of the gustatory pathways are discussed, as they may relate to this patient's visual complaint.