Cavernous Malformation of the Optic Nerve and Chiasm: Prompt Suspicion and Surgery Matter.

BACKGROUND: Cavernous malformations (CMs) of the optic nerve and chiasm are extremely rare, accounting for less than 1% of all intracranial CMs. Acute, subacute, or progressive visual loss from CM may occur with or without hemorrhage. Prompt surgical excision of the CM offers the best hope to improve or stabilize vision. Given its rarity, optic nerve and chiasm CMs may not be readily suspected. We provide 3 cases of optic nerve and chiasm CM, highlighting key neuroimaging features and the importance of expedited intervention. METHODS: Case records of the neuro-ophthalmology clinics of the Bascom Palmer Eye Institute and the University of Colorado, and literature review of reported cases of optic CM. RESULTS: A 49-year-old woman reported acute progressive painless vision loss in the right eye. MRI showed a suprasellar mass with heterogeneity in signal involving the right prechiasmatic optic nerve. Surgical excision of the CM 5 days after onset of visual loss improved vision from 20/300 to 20/30. A 29-year-old woman with acute painless blurred vision in the right eye had anterior chiasmal junctional visual field defects corresponding to a heterogeneously minimally enhancing mass with blood products enlarging the optic chiasm and proximal right optic nerve. Surgical excision of the CM 8 weeks after onset of visual loss improved vision from 20/40 to 20/15 with improved visual fields. A 33-year-old woman with a history of familial multiple CMs, diagnosed at age 18, reported new-onset severe headache followed by blurred vision. MRI showed a hemorrhagic lesion of the optic chiasm and right optic tract. She was 20/20 in each eye with a reported left superior homonymous hemianopia. No intervention was recommended. Vision of the right eye worsened to 20/400 2 months later. The patient was followed over 13 years, and the MRI and visual function remained unchanged. Literature review yielded 87 optic CM cases occurring across gender and nearly all ages with visual loss and headache as the most common presenting symptoms. Optic chiasm is the most common site of involvement (79%). Nearly 95% of reported CM cases were treated with surgery with 81% with improved vision and 1% with worsened vision. CONCLUSION: MRI features are critical to the diagnosis of optic nerve and chiasm CM and may mimic other lesions. A high index of suspicion by the neuro-ophthalmologist and neuroradiologist leads to early recognition and intervention. Given optic CM displaces and does not infiltrate neural tissue, expedited surgical resection by a neurosurgeon after consideration of other diagnostic possibilities improves visual function in most cases.

Compartmental Differences in Macular Retinal Ganglion Cell Function.

Purpose: The purpose of this study was to investigate local differences of macular retinal ganglion cell (RGC) function by means of the steady-state pattern electroretinogram (SS-PERG). Methods: SS-PERGs were recorded in healthy subjects (n = 43) in response to gratings (1.6 c/deg, 15.63 reversals/s, and 98% contrast) presented on an LED display (800 cd/m2, 12.5 degrees eccentricity at 30 cm viewing distance) partitioned in triangular sectors (inferior [I]; nasal [N]; superior [S]; and temporal [T]) or concentric regions (central [C] and annulus [A]). For each partition, response amplitude (nV), amplitude adaptation (% change over recording time), phase/latency (deg/ms), and oscillatory potentials (OPs) amplitude (root mean square [RMS] nV) were measured. Data were analyzed with Generalized Estimating Equation (GEE) statistics. Results: Amplitude differed (P < 0.001) between sectors (I: 254 nV; N: 328 nV; S: 275 nV; T: 264 nV; and N>T, I) as well as concentrically (C: 684 nV; A: 323 nV; and C>A). Latency did not differ between sectors (range = 53-54 ms, P = 0.45) or concentrically (range = 51-51 ms, P = 0.7). Adaptation did not differ (P = 0.66) concentrically (C: -19% and A: -22%) but differed (P = 0.004) between sectors (I: +25% and S: -29%). The OP amplitude did not differ (P = 0.5) between sectors (range = 63-73 nV) as well as concentrically (range = 82-90 nV, P = 0.3). Conclusions: Amplitude profiles paralleled RGC densities from histological studies. Adaptation profile suggested greater autoregulatory challenge in the inferior retina. Latency profile may reflect axonal conduction time to the optic nerve head assuming a direct relationship between axon length and its size/velocity. Location-independent OPs may reflect preganglionic activity. Translational Relevance: Normal macular RGC function displays local differences that may be related to local vulnerability in optic nerve disorders.

Non-invasive Assessment of Central Retinal Artery Pressure: Age and Posture-dependent Changes.

Purpose: Assessment of Ocular Perfusion Pressure (OPP) requires estimation of the Mean Central Retinal Artery Pressure (MCRAP) [OPP = MCRAP-IOP]. In a seated position, MCRAP is currently estimated as 2/3 of the Mean Arterial Pressure (MAP) to account for the hydrostatic reduction of MAP at eye level. We tested a surrogate method for direct MCRAP assessment by measuring MAP with Arm-Up and cuff at eye level (AUMAP) at different postures and ages. Methods: MAP and AUMAP were assessed in a mixed population of 136 subjects (mean age 44 ± 17.39 years) including healthy participants (N = 30) and patients with optic neuropathies (Glaucoma suspects, N = 14; Open-Angle Glaucoma, N = 26, LHON, N = 19; MS, N = 47) not expected to alter systemic blood pressure. None of the subjects had history of carotid stenosis or pharmacological treatment to regulate blood pressure. AUMAP was also tested in two subgroups in supine (N = 42) and -10° Head Down body Tilt position (HDT, N = 46). Results: In the seated position, both 2/3MAP and AUMAP increased with increasing age, however with steeper (2x) slope for AUMAP (P < .0001). With decreasing angle of body tilt, AUMAP increased while MAP decreased. The mean AUMAP/MAP ratio (posture coefficient) was, seated, 0.73 (SE 0.003); supine, 0.90 (SE 0.005); HDT, 0.97 (SE 0.005). In the seated position only, the AUMAP/MAP ratio significantly increased with age (P < .0001). Mean posture coefficients obtained with AUMAP were in the range of those based on either direct ophthalmodynamometric measurements or hydrostatic estimations. Conclusions: Surrogate measurement of MCRAP in individual subjects is feasible using the simple AUMAP approach that provides a straightforward estimation of OPP (OPP = AUMAP - IOP) at different body postures. The standard method OPP = 2/3*MAP-IOP in the seated posture underestimates OPP at older ages. Clinical estimation of OPP would benefit from the use of AUMAP, in particular for head-down postures.

Investigating Vascular Complexity and Neurogenic Alterations in Sectoral Regions of the Retina in Patients With Cognitive Impairment.

Evidence is accumulating that cognitive function, and visual impairment may be related. In this pilot study, we investigated whether multifractal dimension and lacunarity analyses performed in sectoral regions of the retina may reveal changes in patients with cognitive impairment (CI) that may be masked in the study considering the whole retinal branching pattern. Prospective age-matched subjects (n = 69) with and with no CI and without the presence of any ophthalmic history were recruited (age > 55+ years). The Montreal Cognitive Assessment (MoCA) was used to measure CI, and full-field electroretinogram (ERG) was performed. Also, visual performance exams were conducted using the Rabin cone contrast test (CCT). Quantification of the retinal structure was performed in retinal fundus images [45 o field of view (FOV), optic disk centered] with excellent quality for all individuals [19 healthy controls (HC) and 20 patients with CI] after evaluating the inclusion and exclusion criteria in all study participants recruited (n = 69). The skeletonized vasculature network that comprised the whole branching pattern observable in the full 45° FOV was obtained for each image and divided into nine equal regions (superotemporal, superior, superonasal, macular, optic disk, nasal, inferotemporal, inferior, and inferonasal). The multifractal behavior was analyzed by calculating the generalized dimension Dq (Do, D1, and D2), the lacunarity parameter (Λ), and singularity spectrum f(α) in the nine sectoral skeletonized images as well as in the skeletons that comprised the whole branching pattern observable in the full 45° FOV. The analyses were performed using the ImageJ program together with the FracLac plug-in. Independent sample t-tests or Mann Whitney U test and Pearson correlation coefficient were used to find associations between all parameters in both groups. The effect size (Cohen's d) of the difference between both groups was also assessed. A p-value < 0.05 was considered statistically significant. Significant correlations between multifractal and Λ parameters with the MoCA and implicit time ERG-parameter were observed in the regional analysis. In contrast, no trend was found when considering the whole retinal branching pattern. Analysis of combined structural-functional parameters in sectoral regions of the retina, instead of individual retinal biomarkers, may provide a useful clinical marker of CI.

Marcus Gunn jaw winking syndrome in a 6-year-old boy: a new observation.

We report the case of a 6-year-old boy with bilateral Marcus Gunn jaw winking syndrome with a left hypotropia in primary gaze that decreased in magnitude during jaw thrust to the contralateral side. To our knowledge, this is a new observation with regard to the ocular motility disturbances in this syndrome.

Long-term PERG monitoring of untreated and treated glaucoma suspects.

PURPOSE: To investigate long-term structural and functional progression of untreated and treated glaucoma suspects (UGS and TGS). METHODS: Retrospective analysis of serial steady-state pattern electroretinogram (PERG), mean retinal nerve fiber layer thickness (RNFLT), and standard automated perimetry mean deviation (SAP-MD) in UGS (N = 20) and TGS (N = 18). Outcome measures were the rates of change (linear regression slopes) of PERG amplitude, PERG phase, mean RNFLT, and SAP-MD over 9.8 ± 1.3 years (15.6 ± 4.2 visits). RESULTS: The number of patients with significant (P < 0.05) progression slopes for PERG amplitude, PERG phase, RNFLT, and SAP-MD was, respectively, UGS: 5, 0, 4, 2; TGS: 8, 2, 6, 5. In UGS, outcome measures were not correlated with each other. In TGS, both PERG amplitude and RNFLT were significantly (P < 0.05) correlated with SAP-MD (R ≥ 0.58), while PERG amplitude and RNFLT were not correlated with each other (R = 0.43, P = 0.064). The rate of change of SAP-MD was predicted (P < 0.05) by a linear combination of RNFLT slope and PERG amplitude slope. CONCLUSIONS: Results substantiate and extend previous results showing that steady-state PERG amplitude progressively decreased over time in a proportion of glaucoma suspects, with relatively steeper slope in TGS compared to UGS. RNFLT progression also had a steeper slope in TGS compared to UGS; however, progressions of PERG amplitude and RNFLT were not significantly correlated. Both PERG progression and RNFLT progression independently contribute to prediction of visual field progression.

Distinguishing cognitive impairment by using singularity spectrum and lacunarity analysis of the retinal vascular network.

The development of effective therapies for cognitive impairment (CI), especially due to Alzheimer's disease, demands diagnosing the condition during the prodromal phase. The diagnosis of CI involves expensive and invasive methods, such as positron emission tomography and cerebrospinal fluid assessment via spinal tap. Hence, a comparatively lower cost and noninvasive method of diagnosis is imperative. The human retina is an extension of the brain characterized by similarities in vascular and neural structures. The complications of CI are not only limited to the brain but also affect the retina for which the loss of retinal ganglion cells has been associated with neurodegeneration in the brain. The loss of retinal ganglion cells in individuals with CI may be related to reduced vascular demand and a potential remodeling of the retinal vascular branching complexity. Retinal imaging biomarkers may provide a low cost and noninvasive alternative for the diagnosis of CI. In this study, the retinal vascular branching complexity of patients with CI was characterized using the singularity spectrum multifractal dimension and lacunarity parameter. A reduced vascular branching complexity was observed in subjects with CI when compared to age- and sex-matched cognitively healthy controls. Significant associations were also found between retinal vascular and functional parameters.

Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina.

Previous studies have demonstrated that cognitive impairment (CI) is not limited to the brain but also affects the retina. In this pilot study, we investigated the correlation between the retinal vascular complexity and neurodegenerative changes in patients with CI using a low-cost multimodal approach. Quantification of the retinal structure and function were conducted for every subject (n = 69) using advanced retinal imaging, full-field electroretinogram (ERG) and visual performance exams. The retinal vascular parameters were calculated using the Singapore Institute Vessel Assessment software. The Montreal Cognitive Assessment was used to measure CI. Pearson product moment correlation was performed between variables. Of the 69 participants, 32 had CI (46%). We found significantly altered microvascular network in individuals with CI (larger venular-asymmetry factor: 0.7 ± 0.2) compared with controls (0.6 ± 0.2). The vascular fractal dimension was lower in individuals with CI (capacity, information and correlation dimensions: D0, D1, and D2 (mean ± SD): 1.57 ± 0.06; 1.56 ± 0.06; 1.55 ± 0.06; age 81 ± 6years) vs. controls (1.61 ± 0.03; 1.59 ± 0.03; 1.58 ± 0.03; age: 80 ± 7 years). Also, drusen-like regions in the peripheral retina along with pigment dispersion were noted in subjects with mild CI. Functional loss in color vision as well as smaller ERG amplitudes and larger peak times were observed in the subjects with CI. Pearson product moment correlation showed significant associations between the vascular parameters (artery-vein ratio, total length-diameter ratio, D0, D1, D2 and the implicit time (IT) of the flicker response but these associations were not significant in the partial correlations. This study illustrates that there are multimodal retinal markers that may be sensitive to CI decline, and adds to the evidence that there is a statistical trend pointing to the correlation between retinal neuronal dysfunction and microvasculature changes suggesting that retinal geometric vascular and functional parameters might be associated with physiological changes in the retina due to CI. We suspect our analysis of combined structural-functional parameters, instead of individual biomarkers, may provide a useful clinical marker of CI that could also provide increased sensitivity and specificity for the differential diagnosis of CI. However, because of our study sample was small, the full extent of clinical applicability of our approach is provocative and still to be determined.

Investigating the Fractal Dimension of the Foveal Microvasculature in Relation to the Morphology of the Foveal Avascular Zone and to the Macular Circulation in Patients With Type 2 Diabetes Mellitus.

In this study, we examined the relationship between the fractal dimension (FD), the morphology of the foveal avascular zone (FAZ) and the macular circulation in healthy controls and patients with type 2 diabetes mellitus (T2DM) with and with no diabetic retinopathy (DR). Cross-sectional data of 47 subjects were analyzed from a 5-year longitudinal study using a multimodal optical imaging approach. Healthy eyes from nondiabetic volunteers (n = 12) were selected as controls. Eyes from patients with T2DM were selected and divided into two groups: diabetic subjects with mild DR (MDR group, n = 15) and subjects with DM but without DR (DM group, n = 20). Our results demonstrated a higher FD in the healthy group (mean, 1.42 ± 0.03) than in the DM and MDR groups (1.39 ± 0.02 and 1.35 ± 0.03, respectively). Also, a bigger perimeter, area, and roundness of the FAZ were found in MDR eyes. A significant difference in area and perimeter (p ≤ 0.005) was observed for the MDR group supporting the enlargement of the FAZ due to diabetic complications in the eye. A moderate positive correlation (p = 0.014, R2 = 43.8%) between the FD and blood flow rate (BFR) was only found in the healthy control group. The BFR calculations revealed the lowest values in the MDR group (0.98 ± 0.27 µl/s vs. 1.36 ± 0.86 µl/s and 1.36 ± 0.57 µl/sec in the MDR, DM, and healthy groups, respectively, p = 0.2). Our study suggests that the FD of the foveal vessel arborization could provide useful information to identify early morphological changes in the retina of patients with T2DM. Our results also indicate that the enlargement and asymmetry of the FAZ might be related to a lower BFR because of the DR onset and progression. Interestingly, due to the lack of FAZ symmetry observed in the DM and MDR eyes, it appears that the distribution of flow within the retinal vessels loses complexity as the vascular structures distributing the flow are not well described by fractal branching. Further research could determine how our approach may be used to aid the diagnosis of retinal neurodegeneration and vascular impairment at the early stage of DR.

Retinal ganglion cell function in recovered optic neuritis: Faster is not better.

OBJECTIVE: To assess residual retinal ganglion cell (RGC) function in patients with recovered optic neuritis (ON) and multiple sclerosis (MS). METHODS: Age-matched controls (C, n = 32) and MS patients (n = 17) with history of ON in one eye but normal visual acuity and color vision were tested with steady-state Pattern Electroretinogram (PERG). Light Emitting Diodes (LED)-generated bar gratings, robust signal averaging and Fourier analysis were used to assess response amplitude and latency. RESULTS: PERG amplitude was similar for C, ON and fellow eyes (FE) (P = 0.4), but PERG latency was shortened in ON by 3.2 ms (P = 0.002) and in FE by 2.0 ms (P = 0.02) and was correlated (P < 0.01) with both Retinal Nerve Fiber Layer (RNFL) and Ganglion Cell Inner Plexiform Layer (GCIPL) thicknesses. PERG latency shortening could be simulated in control subjects (n = 8) by dioptrically blurring the edges of gratings (high spatial frequencies), which reduced activity of parvocellular RGCs with smaller/slower axons. The blurred PERG latency was shorter than baseline by 2.9 ms (P = 0.01). CONCLUSIONS: PERG latency is shortened in both eyes of MS patients with recovered unilateral ON, suggesting relative dysfunction of RGCs with slower axons and sparing of RGCs with faster axons. SIGNIFICANCE: Assessment of PERG latency in MS and ON may help identifying and monitoring RGC dysfunction. PERG latency shortening in FE suggests primary retinopathy in MS.

Relationship between the morphology of the foveal avascular zone, retinal structure, and macular circulation in patients with diabetes mellitus.

Diabetic Retinopathy (DR) is an extremely severe and common degenerative disease. The purpose of this study was to quantify the relationship between various parameters including the Foveal Avascular Zone (FAZ) morphology, retinal layer thickness, and retinal hemodynamic properties in healthy controls and patients with diabetes mellitus (DM) with and with no mild DR (MDR) using Spectral-Domain Optical Coherence Tomography (Spectralis SDOCT, Heidelberg Engineering GmbH, Germany) and the Retinal Function Imager (Optical Imaging, Ltd., Rehovot, Israel). Our results showed a higher FAZ area and diameter in MDR patients. Blood flow analysis also showed that there is a significantly smaller venous blood flow velocity in MDR patients. Also, a significant difference in roundness was observed between DM and MDR groups supporting the development of asymmetrical FAZ expansion with worsening DR. Our results suggest a potential anisotropy in the mechanical properties of the diabetic retina with no retinopathy that may trigger the FAZ elongation in a preferred direction resulting in either thinning or thickening of intraretinal layers in the inner and outer segments of the retina as a result of autoregulation. A detailed understanding of these relationships may facilitate earlier detection of DR, allowing for preservation of vision and better clinical outcomes.