To characterize the density and distribution of the radial peripapillary capillary plexus (RPCP) and its relationship with retinal nerve fiber layer (NFL) thickness in healthy subjects.
Using ...spectral-domain optical coherence tomography (OCT), split-spectrum amplitude decorrelation angiography algorithm and automated montaging, wide-field OCT angiography (OCTA) was used to measure the RPCP capillary density (CD) and NFL thickness. Polar sector-average CD and thickness maps were also created on each eye.
Wide-field OCTA (8 × 8 mm) in 10 healthy eyes from 10 subjects demonstrated the distribution of the RPCP throughout the posterior pole. RPCP-CD decreases with distance from the disc, but along the arcuate nerve fiber bundles relatively dense (> half maximum density) RPCP extends more than 5 mm from the disc and includes regions superior to and inferior to the macula. The RPCP-CD and NFL thickness are highly correlated (R2 = 0.85, P < 0.001) and fit well with a nonlinear stacked-layer model. The model fit suggests that the RPCP is present when the NFL is thicker than 17.9 μm and reaches a ceiling area density of 84% and that the RPCP has an apparent volume density of 19% at the current instrument transverse resolution. This indicates that capillary overlap can be expected to occur when NFL thickness reaches 40 μm.
The wide distribution of dense overlapping RPCP suggests that wider (up to 8 mm vertical and 7 mm horizontal) OCTA scans may be better investigate capillary loss in the early stages of glaucoma or other optic neuropathies.
Purpose
Diabetic retinopathy (DR) can lead to significant vision loss and blindness and has a particularly high prevalence in patients with type 1 diabetes (DM1). In this study, we investigate ...quantitative differences in optical coherence tomography angiography (OCTA) data between DM1 patients with no or mild signs of retinopathy and non‐diabetic subjects.
Methods
Optical coherence tomography angiography (OCTA) imaging was performed on DM1 patients with no or mild nonproliferative diabetic retinopathy and healthy, age‐matched controls. Parafoveal vessel density and foveal avascular zone (FAZ) area in the deep capillary plexus (DCP) and superficial capillary plexus (SCP) were calculated with automated quantification software and compared between patient cohorts.
Results
A significant decrease in parafoveal vessel density was seen in the DCP of DM1 patients compared to non‐diabetic controls (57.0 ± 3.3% versus 60.7 ± 2.4%, p < 0.001). There was no significant difference in SCP parafoveal vessel density, DCP FAZ area, or SCP FAZ area between cohorts.
Conclusion
M1 patients with no or mild signs of retinopathy have reduced parafoveal vessel density in the DCP on OCTA when compared to non‐diabetic controls. These OCTA findings suggest that parafoveal capillary nonperfusion is an early process in DM1‐related retinal changes and occurs initially at the level of the DCP. Further investigation is needed to understand the prognostic role of these vascular changes.
IMPORTANCE: Recent studies have linked a vision-threatening maculopathy with long-term use of pentosan polysulfate sodium (PPS). OBJECTIVE: To evaluate the disease course in PPS-associated ...maculopathy after drug cessation. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case series, patients diagnosed with PPS-associated maculopathy with at least 6 months of follow-up after drug cessation who were treated at the Emory Eye Center, Atlanta, Georgia, or the Casey Eye Institute, Portland, Oregon, were included. Data were collected from April 2014 through November 2019. MAIN OUTCOMES AND MEASURES: Change in visual acuity and retinal imaging characteristics over time. RESULTS: Of the 11 included patients, all were female, and the median (interquartile range IQR) age was 53 (44-63) years. Participants had a baseline visit at a median (IQR) of 2 (0-4) months after drug cessation and were subsequently observed for a median (IQR) of 12 (8-26) months. The median (IQR) cumulative PPS exposure was 1.97 (1.55-2.18) kg. No eyes exhibited a demonstrable improvement in disease after discontinuing PPS. A total of 9 of 11 patients (82%) reported worsening visual symptoms at the final visit. The mean (SD) logMAR visual acuity was 0.14 (0.23) and 0.14 (0.34) at the baseline and final visit, respectively. Visual acuity improved by 2 or more Snellen lines in 1 eye (5%) and declined by 2 or more Snellen lines in 2 eyes of 1 patient (9%). There was evolution in the pattern of fundus autofluorescence changes and/or optical coherence tomography findings in all eyes. A total of 17 eyes (77%) exhibited expansion of the area of involved tissue. A total of 7 eyes (32%) had macular retinal pigment epithelium atrophy at the baseline visit, and atrophy enlarged after discontinuation of PPS in all 7 eyes, with a median (IQR) growth rate of 0.32 (0.13-0.38) mm per year. CONCLUSIONS AND RELEVANCE: These retrospective data among 11 patients suggest PPS-associated maculopathy continues to evolve after drug cessation for at least 10 years. In some cases, progressive retinal pigment epithelium atrophy encroaches on the foveal center and thus may pose a long-term threat to central vision.
Best disease (BD) is an inherited degenerative disease of the human macula that results in progressive and irreversible central vision loss. It is caused by mutations in the retinal pigment ...epithelium (RPE) gene BESTROPHIN1 (BEST1), which, through mechanism(s) that remain unclear, lead to the accumulation of subretinal fluid and autofluorescent waste products from shed photoreceptor outer segments (POSs). We employed human iPS cell (hiPSC) technology to generate RPE from BD patients and unaffected siblings in order to examine the cellular and molecular processes underlying this disease. Consistent with the clinical phenotype of BD, RPE from mutant hiPSCs displayed disrupted fluid flux and increased accrual of autofluorescent material after long-term POS feeding when compared with hiPSC-RPE from unaffected siblings. On a molecular level, RHODOPSIN degradation after POS feeding was delayed in BD hiPSC-RPE relative to unaffected sibling hiPSC-RPE, directly implicating impaired POS handling in the pathophysiology of the disease. In addition, stimulated calcium responses differed between BD and normal sibling hiPSC-RPE, as did oxidative stress levels after chronic POS feeding. Subcellular localization, fractionation and co-immunoprecipitation experiments in hiPSC-RPE and human prenatal RPE further linked BEST1 to the regulation and release of endoplasmic reticulum calcium stores. Since calcium signaling and oxidative stress are critical regulators of fluid flow and protein degradation, these findings likely contribute to the clinical picture of BD. In a larger context, this report demonstrates the potential to use patient-specific hiPSCs to model and study maculopathies, an important class of blinding disorders in humans.
Self-inflicted damage to the retina using handheld lasers is a growing and underrecognized form of self-harm. Here was share retinal images from two patients with histories of major depressive ...disorder and self-harm behaviors that ultimately resulted in legal blindness. Mental health providers should be aware of this clinical entity as they are in the best position to screen for laser pointer access in at risk individuals and prevent permanent vision loss.
IMPORTANCE: Blood-brain barrier disruption (BBBD) is a systemic therapy for malignant central nervous system (CNS) tumors that has been linked to poorly understood pigmentary maculopathy. OBJECTIVES: ...To examine the rate of and risk factors for the development of BBBD-associated maculopathy and to assess whether there can be visually significant progression after completion of systemic therapy. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case series, data from February 1, 2006, through December 31, 2019, were collected from patients treated with osmotic BBBD at a single tertiary referral center who had subsequent ophthalmic evaluation. EXPOSURES: Treatment with BBBD therapy for any malignant CNS tumor. MAIN OUTCOMES AND MEASURES: Rate and potential risk factors for developing BBBD-associated maculopathy and changes in visual acuity and retinal imaging characteristics after completion of BBBD therapy. RESULTS: Of 283 patients treated with BBBD and chemotherapy for a CNS malignant neoplasm, 68 (mean SD age, 46.0 17.9 years; 25 38.5% female) had an ophthalmic examination after starting systemic therapy. After excluding 3 patients because of bilateral media opacities, pigmentary maculopathy was present in 32 of 65 patients (49.2%) treated with BBBD. The number of BBBD treatment sessions, but not age, CNS malignant cancer type, or systemic chemotherapy agent, was associated with maculopathy development (odds ratio, 1.30; 95% CI, 1.12-1.50; P = .001). After completion of BBBD therapy, progressive enlargement of geographic atrophy occurred in 5 eyes of 3 patients, and choroidal neovascularization developed in 1 eye. CONCLUSIONS AND RELEVANCE: In this case series, an association was found between BBBD-related maculopathy and the number of BBBD treatment sessions, suggesting a dose-dependent effect. In some cases, maculopathy progression, including enlargement of geographic atrophy, occurred years after completion of systemic therapy. These findings may have important implications for patient education and ophthalmic monitoring.
Microphthalmia-associated transcription factor (MITF) is a master regulator of pigmented cell survival and differentiation with direct transcriptional links to cell cycle, apoptosis and pigmentation. ...In mouse, Mitf is expressed early and uniformly in optic vesicle (OV) cells as they evaginate from the developing neural tube, and null Mitf mutations result in microphthalmia and pigmentation defects. However, homozygous mutations in MITF have not been identified in humans; therefore, little is known about its role in human retinogenesis. We used a human embryonic stem cell (hESC) model that recapitulates numerous aspects of retinal development, including OV specification and formation of retinal pigment epithelium (RPE) and neural retina progenitor cells (NRPCs), to investigate the earliest roles of MITF. During hESC differentiation toward a retinal lineage, a subset of MITF isoforms was expressed in a sequence and tissue distribution similar to that observed in mice. In addition, we found that promoters for the MITF-A, -D and -H isoforms were directly targeted by Visual Systems Homeobox 2 (VSX2), a transcription factor involved in patterning the OV toward a NRPC fate. We then manipulated MITF RNA and protein levels at early developmental stages and observed decreased expression of eye field transcription factors, reduced early OV cell proliferation and disrupted RPE maturation. This work provides a foundation for investigating MITF and other highly complex, multi-purposed transcription factors in a dynamic human developmental model system.
The purpose of this study was to analyze the natural history and phenotypic overlap of patients with microcephaly and a chorioretinopathy or familial exudative vitreoretinopathy (FEVR) ocular ...phenotype caused by mutations in KIF11, TUBGCP4, or TUBGCP6.
Patients diagnosed with congenital microcephaly and chorioretinopathy or FEVR were included. Molecular investigations consisted of targeted genetic sequencing. Data from medical records, ophthalmologic examination and imaging, electroretinography, and visual fields were analyzed for systemic and ophthalmic features and evidence of posterior segment disease progression.
Twelve patients from 9 families were included and had a median of 8 years of follow-up. Nine patients had KIF11 variants, two had heterozygous TUBGCP6 variants, and one had heterozygous variants in TUBGCP4. All patients had reduced visual function and multiple individuals and families showed features of both chorioretinopathy and FEVR. Progression of posterior segment disease was highly variable, with some degree of increased atrophy of the macula or peripheral retina or increased vitreoretinal traction observed in 9 of 12 patients.
Microcephaly due to mutations in KIF11, TUBGCP4, or TUBGCP6 can be associated with retinal disease on a spectrum from chorioretinal atrophy to FEVR-like posterior segment changes. Visually significant disease progression can occur and patients should be monitored closely by a team experienced in ophthalmic genetics.
Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder that may have anterior visual pathway involvement. In this study, we compare the macular structure of patients with ALS to ...healthy controls, and examine correlations between macular sub-layer thickness measurements and pulmonary function tests and disease duration. ALS patients underwent optical coherence tomography (OCT) imaging to obtain macular cube scans of the right eye. Macular cube OCT data from age-matched healthy subjects were provided by the OCT reading center. Semi-automated retinal segmentation software was used to quantify macular sub-layers. Pulmonary function tests and time since symptom onset were collected retrospectively from the electronic medical records of ALS patients. Macular retinal nerve fiber layer was significantly thinner in ALS patients compared to healthy controls (P < 0.05). Total macular and other sub-layer thicknesses were not reduced in the ALS cohort. Macular retinal nerve fiber layer thickness positively correlated with forced vital capacity % predicted and forced expiratory volume in 1 second % predicted (P < 0.05). In conclusion, analysis of OCT measurements supports the involvement of the anterior visual pathway in ALS. Subtle structural thinning in the macular retinal nerve fiber layer correlates with pulmonary function tests.
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