Purpose: To evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA). Methods: In this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly. Results: After sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02). Conclusions: The changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity.
High-risk coronary plaques have been considered predictive of adverse cardiac events. Both wall shear stress (WSS) in patients with hemodynamically significant lesions and optical coherence tomography (OCT) -verified thin-cap fibroatheroma (TCFA) are associated with plaque rupture, the most common underlying mechanism of acute coronary syndrome. The aim of the study was to test the hypothesis that invasive coronary angiography-based high WSS is associated with the presence of TCFA detected by OCT in obstructive lesions. From a prospective study of patients who underwent OCT examination for angiographically obstructive lesions (Yellow II), we selected patients who had two angiographic projections to create a 3-dimensional reconstruction model to allow assessment of WSS. The patients were divided into 2 groups according to the presence and absence of TCFA. Mean WSS was assessed in the whole lesion and in the proximal, middle and distal segments. Of 70 patients, TCFA was observed in 13 (19%) patients. WSS in the proximal segment (WSSproximal) (10.20 [5.01, 16.93Pa]) and the whole lesion (WSSlesion) (12.37 [6.36, 14.55Pa]) were significantly higher in lesions with TCFA compared to WSSproximal (5.84 [3.74, 8.29Pa], p = 0.02) and WSSlesion (6.95 [4.41, 11.60], p = 0.04) in lesions without TCFA. After multivariate analysis, WSSproximal was independently associated with the presence of TCFA (Odds ratio 1.105; 95%CI 1.007–1.213, p = 0.04). The optimal cutoff value of WSSproximal to predict TCFA was 6.79 Pa (AUC: 0.71; sensitivity: 0.77; specificity: 0.63 p = 0.02). Our results demonstrate that high WSS in the proximal segments of obstructive lesions is an independent predictor of OCT-verified TCFA.
by
Erin A. Boese;
Nieraj Jain;
Yali Jia;
Catie L. Schlechter;
Cary O. Harding;
Simon S. Gao;
Rachel C. Patel;
David Huang;
Richard G. Weleber;
Melanie B. Gillingham;
Mark E. Pennesi
Objective: To assess long-term effects of genotype on chorioretinopathy severity in subjects with mitochondrial trifunctional protein (MTP) disorders. Design: Retrospective case series. Participants: Consecutive patients with MTP disorders evaluated at a single center from 1994 to 2015, including 18 subjects with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 subjects with trifunctional protein deficiency (TFPD). Methods: Local records from all visits were reviewed. Every subject underwent complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine subjects underwent ancillary fundoscopic imaging including optical coherence tomography (OCT) and OCT angiography. Main Outcome Measures: The primary outcome measure was best-corrected visual acuity (logMAR) at the final visit. Secondary outcome measures included spherical equivalent refraction, electroretinogram (ERG) b-wave amplitudes, and qualitative imaging findings. Results: Subjects were followed for a median of 5.6 years (range 0.3–20.2). The median age of LCHADD subjects at initial and final visits was 2.3 and 11.9 years, while the median age for TFPD subjects at initial and final visits was 4.7 and 15.5 years. Four long-term survivors over the age of 16 years were included (three subjects with LCHADD and one subject with TFPD). LCHADD subjects demonstrated a steady decline in visual acuity from an average logMAR of 0.23 (Snellen equivalent 20/34) at baseline to 0.42 (Snellen equivalent 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow up. Subjects with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. ERG findings support the more severe clinical profile of LCHADD subjects compared with TFPD; the function of both rods and cones are diffusely attenuated in LCHADD but within normal limits for TFPD subjects. Conclusions: Despite improved survival with early diagnosis, medical management, and dietary treatment, subjects with the LCHADD subtype of MTP disorder continue to develop visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.
by
Baptiste Coudrillier;
Diogo M. Geraldes;
Nghia T. Vo;
Robert Atwood;
Christina Reinhard;
Ian C. Campbell;
Yazdan Raji;
Julie Albon;
Richard L. Abel;
Christopher Ethier
The lamina cribrosa (LC) is a complex mesh-like tissue in the posterior eye. Its biomechanical environment is thought to play a major role in glaucoma, the second most common cause of blindness. Due to its small size and relative inaccessibility, high-resolution measurements of LC deformation, important in characterizing LC biomechanics, are challenging. Here we present a novel noninvasive imaging method, which enables measurement of the three-dimensional deformation of the LC caused by acute elevation of intraocular pressure (IOP). Posterior segments of porcine eyes were imaged using synchrotron radiation phase contrast micro-computed tomography (PC μCT) at IOPs between 6 and 37 mmHg. The complex trabecular architecture of the LC was reconstructed with an isotropic spatial resolution of 3.2 μm. Scans acquired at different IOPs were analyzed with digital volume correlation (DVC) to compute full-field deformation within the LC. IOP elevation caused substantial tensile, shearing and compressive devformation within the LC, with maximum tensile strains at 30 mmHg averaging 5.5%, and compressive strains reaching 20%. We conclude that PC μCT provides a novel high-resolution method for imaging the LC, and when combined with DVC, allows for full-field 3D measurement of ex vivo LC biomechanics at high spatial resolution.
Inner retinal thinning on optical coherence tomography (OCT) occurring through retrograde trans-synaptic degeneration is an increasingly recognized phenomenon, even in acquired retro-chiasmal brain lesions. We describe a man with stable visual field defects from multiple bilateral posterior circulation infarctions, who had ganglion cell complex (GCC) thinning on macular OCT that corresponded precisely with his visual field defects. In contrast to previous reports indicating that peripapillary retinal nerve fiber layer (RNFL) changes are important in detecting this phenomenon, the peripapillary RFNL thickness and the optic disc appearance of our patient were relatively unaffected. Our case contributes to the growing body of evidence that retrograde trans-synaptic degeneration can manifest as isolated macular OCT findings.
We were honored last year to have been invited by the Taiwan Ophthalmological Society as their guests at the 60th Anniversary Meeting, an extraordinary professional, academic, intellectual and social event. We were doubly honored when we were asked by the Editor-In-Chief David Hui-Kang Ma and his Editorial Board of the Taiwan Journal of Ophthalmology to co-edit this special edition in the journal on neuro-ophthalmologic topics. Neuro-ophthalmology has always been an essential part of the training of every ophthalmologist worldwide. Irrespective of how specialized an ophthalmologist becomes in even the most tiny of portions of the eye, there can always be a neuro-ophthalmologic cause lurking behind a patient's seemingly straightforward presentation. Ophthalmologists are skilled in direct inspection of the eye and are used to actually seeing pathology rather than inferring it. Not seeing does not mean not knowing, however, and ophthalmologists can overcome their concerns by remembering their training in neuro-ophthalmology and continuing to refresh their education throughout their careers. Indeed, every ophthalmologist should be not only comfortable but also interested in that part of the visual system that lets the eye do what it needs to do so well.
Purpose
To correlate the clinical and histopathologic features of Best vitelliform macular dystrophy (BVMD).
Methods
Two eyes were obtained postmortem from a patient with BVMD. The patient’s clinical information was reviewed. Series sections of the globes were performed and sequentially stained with hematoxylin-eosin, periodic acid-Schiff or Masson trichrome. A section of the left macula was submitted for electron microscopic processing. Histopathologic findings were reconstructed in a scaled two-dimensional map and compared with fundus photography, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) images.
Results
The macular lesion of the right eye was identified as a well-demarcated region with pigment, elevated submacular yellow material and subretinal fluid. This corresponded histopathologically to a well-circumscribed area of RPE hyperplasia, accumulation of lipofuscin in the RPE, deposition of granular material in the photoreceptors, macrophages and drusen. The left eye displayed a 1 disc diameter chorioretinal scar with surrounding shallow fluid and submacular pigment. This corresponded to RPE changes and a fibrocellular proliferation in the choriocapillaris.
Conclusion
Histopathologic mapping revealed retinal edema, RPE abnormalities, drusen and a chorioretinal scar in BVMD that correlated with the fundus, FFA, FAF and OCT findings.
With fewer than 100 peer-reviewed cases reported in the world to date, the underlying etiology of torpedo maculopathy has remained elusive. In this literature review, we provide new evidence to better support, reject and unify claims regarding cause, diagnosis, and proper clinical management of this disease. We reviewed 44 case reports and case series, which included 77 patients (after exclusions). We additionally introduced 3 new cases from our clinical practice for a total of 80 cases. Ages at presentation ranged from 6 months old to 73 years old (mean: 24.2 years old). The nasal aspects of torpedo maculopathy lesions pointed toward the optic disc and localized to a kite-shaped region of the temporal macula, correlating with the anatomic junction of the superior arcuate, inferior arcuate, and papillomacular bundles of retinal nerve fiber layer distribution. No patterns were observed among the temporal aspects of the lesions. These findings support a congenital etiology of torpedo maculopathy and a possible influence of the retinal nerve fiber layer in the development of mature retinal pigment epithelium.
Glaucoma is the leading cause of irreversible blindness worldwide. Recently, estrogen deficiencies caused by early menopause, alterations in estrogen signaling via mutations in estrogen receptors, and polymorphisms along estrogen metabolic pathways have all been linked to an increased risk of developing glaucoma. Here, we examined how menopause and age impact visual function and retinal structure in an experimental model of glaucoma. Young (3–4 months) and aged (9–10 months) female Brown Norway rats were divided into pre- and post-menopausal cohorts by surgically inducing menopause via ovariectomy (OVX). After six weeks, ocular hypertension (OHT) was induced unilaterally for a period of eight weeks.
Four cohorts were successfully followed to eight weeks: young sham (n = 8), young OVX (n = 9), aged sham (n = 10), and aged OVX (n = 11) animals. Intraocular pressure (IOP) was monitored weekly in all groups. Prior to inducing OHT (baseline) and at four and eight weeks after inducing OHT, we assessed visual acuity via the optomotor response (OMR) and retinal structure using optical coherence tomography (OCT). OHT decreased the OMR in all cohorts. We found that spatial frequency thresholds decreased by 54% in OVX animals after OHT compared to sham animals after OHT, regardless of age (p < 0.001). We also found thinning of the retinal nerve fiber layer (RNFL) and loss of total retinal thickness after induction of OHT.
Aged animals had more thinning of the RNFL and loss of total retinal thickness compared to young animals (p < 0.001). Overall, OHT caused significant changes in visual function and retinal structure. Observing that OVX in young and aged animals further decreased spatial frequency thresholds after OHT suggests that an estrogen deficiency may intensify visual impairment after OHT.
by
Guorong Li;
Chanyoung Lee;
Vibhuti Agrahari;
Ke Wang;
Iris Navarro;
Joseph M. Sherwood;
Karen Crews;
Sina Farsiu;
Pedro Gonzalez;
Cheng-Wen Lin;
Ashim K. Mitra;
Ross Ethier;
W. Daniel Stamer
Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucoma. The pathophysiology of this condition is poorly understood yet shares similarities with the most common form of glaucoma. Using nanotechnology, we created a mouse model of corticosteroid-induced ocular hypertension. This model functionally and morphologically resembles human ocular hypertension, having titratable, robust, and sustained IOPs caused by increased resistance to aqueous humor outflow. Using this model, we then interrogated the biomechanical properties of the trabecular meshwork (TM), including the inner wall of Schlemm’s canal (SC), tissues known to strongly influence IOP and to be altered in other forms of glaucoma. Specifically, using spectral domain optical coherence tomography, we observed that SC in corticosteroid-treated mice was more resistant to collapse at elevated IOPs, reflecting increased TM stiffness determined by inverse finite element modeling. Our noninvasive approach to monitoring TM stiffness in vivo is applicable to other forms of glaucoma and has significant potential to monitor TM function and thus positively affect the clinical care of glaucoma, the leading cause of irreversible blindness worldwide.