Patterns of retrograde axonal degeneration in the visual system.

Conclusive evidence for existence of acquired retrograde axonal degeneration that is truly trans-synaptic (RTD) has not yet been provided for the human visual system. Convincing data rely on experimental data of lesions to the posterior visual pathways. This study aimed to overcome the limitations of previous human studies, namely pathology to the anterior visual pathways and neurodegenerative co-morbidity. In this prospective, longitudinal cohort retinal optical coherence tomography scans were acquired before and after elective partial temporal lobe resection in 25 patients for intractable epilepsy. Newly developed region of interest-specific, retinotopic areas substantially improved on conventional reported early treatment diabetic retinopathy study (ETDRS) grid-based optical coherence tomography data. Significant inner retinal layer atrophy separated patients with normal visual fields from those who developed a visual field defect. Acquired RTD affected the retinal nerve fibre layer, ganglion cell and inner plexiform layer and stopped at the level of the inner nuclear layer. There were significant correlations between the resected brain tissue volume and the ganglion cell layer region of interest (R = -0.78, P < 0.0001) and ganglion cell inner plexiform layer region of interest (R = -0.65, P = 0.0007). In one patient, damage to the anterior visual pathway resulted in occurrence of microcystic macular oedema as recognized from experimental data. In the remaining 24 patients with true RTD, atrophy rates in the first 3 months were strongly correlated with time from surgery for the ganglion cell layer region of interest (R = -0.74, P < 0.0001) and the ganglion cell inner plexiform layer region of interest (R = -0.51, P < 0.0001). The different time course of atrophy rates observed relate to brain tissue volume resection and suggest that three distinct patterns of retrograde axonal degeneration exist: (i) direct retrograde axonal degeneration; (ii) rapid and self-terminating RTD; and (iii) prolonged RTD representing a 'penumbra', which slowly succumbs to molecularly governed spatial cellular stoichiometric relationships. We speculate that the latter could be a promising target for neuroprotection.

The clinical spectrum of microcystic macular edema.

PURPOSE: Microcystic macular edema (MME), originally described in British literature as microcystic macular oedema (MMO), defines microcysts in the inner nuclear layer (INL) of the retina. Microcystic macular edema was described in multiple sclerosis (MS), but can be found in numerous disorders. The presence of MME has important prognostic and therapeutic implications; however, the differential diagnosis is unknown. This study aimed to describe the clinical spectrum of MME. METHODS: A single-center, retrospective cohort study. A bootstrap analysis was performed to reduce the 5865 patients (22,376 scans), who had undergone OCT imaging between January 2010 and February 2013, to a representative dataset. The presence of MME was rated by independent observers. RESULTS: The dataset consisted of 1368 patients (mean age 62, range, 4-101 years), 2589 eyes and 6449 scans. Microcystic macular edema was present in 133/1303 (10%) of patients and 0/65 (0%) of healthy controls. The interrater agreement for detecting MME was substantial (kappa 0.6) and could be further improved after refining the criteria (kappa 0.8). The clinical spectrum included age-related macular degeneration, epiretinal membranes, postoperative lesions, diabetic retinopathy, vascular occlusion, MS (with/without optic neuritis), optic neuropathy, central serous chorioretinopathy, medication, and miscellaneous causes. The longitudinal pattern of MME was transient (84%) or static. Microcystic macular edema could be associated with an increase or decrease in INL thickness and was predominantly located nasally (48%) and/or temporally (50%). CONCLUSIONS: This study substantially widened the clinical spectrum of MME. Diagnostic criteria were refined and validated. The associated phenotype may imply Müller cell dysfunction within the watershed zone. The longitudinal data and evidence from previous studies suggest follow-up of these patients and their visual function.

A simple sign for recognizing off-axis OCT measurement beam placement in the context of multicentre studies.

PURPOSE: Optical coherence tomography (OCT) allows quantification of the thickness of the retinal nerve fibre layer (RNFL) thickness, a potential biomarker for neurodegeneration. The estimated annual RNFL loss in multiple sclerosis amounts to 2 µm using time domain OCT. The recognition of measurement artifacts exceeding this limit is relevant for the successful use of OCT as a secondary outcome measure in clinical trials. METHODS: Prospective study design. An exploratory pilot study (ring and volume scans) followed by a cohort study (1,980 OCT ring scans). The OCT measurement beam was placed off-axis to the left, right, top and bottom of the subjects pupil and RNFL thickness of these scans were compared to the centrally placed reference scans. RESULTS: Off-axis placement of the OCT measurement beam resulted in significant artifacts in RNFL thickness measurements (95%CI 9µm, maximal size of error 42µm). Off-axis placement gave characteristic patterns of the OCT live images which are not necessarily saved for review. Off-axis placement also causes regional inhomogeneity of reflectivity in the outer nuclear (ONL) and outer plexiform layers (OPL) which remains visible on scans saved for review. CONCLUSION: Off-axis beam placement introduces measurement artifacts at a magnitude which may mask recognition of RNFL loss due to neurodegeneration in multiple sclerosis. The resulting pattern in the OCT live image can only be recognised by the technician capturing the scans. Once the averaged scans have been aligned this pattern is lost. Retrospective identification of this artifact is however possible by presence of regional inhomogeneity of ONL/OPL reflectivity. This simple and robust sign may be considered for quality control criteria in the setting of multicentre OCT studies. The practical advice of this study is to keep the OCT image in the acquisition window horizontally aligned whenever possible.