Ophthalmology science最新文献

Purpose

Lutein (L) and zeaxanthin (Z) are xanthophyll carotenoids that have been promoted to enhance maternal health and infant visual and neurodevelopment. In this study, we determined the effects of prenatal L and Z supplementation on systemic and ocular carotenoid status in the mother and her newborn infant (NCT03750968). This report focuses on the ocular effects of prenatal carotenoid supplementation.

Design

A prospective randomized clinical trial with 47 subjects randomly assigned by 1:1 allocation to receive standard-of-care prenatal vitamins along with 10 mg L and 2 mg Z softgel (Carotenoid Group) or standard-of-care prenatal vitamins with a placebo softgel (Control Group) starting in the first trimester.

Subjects

We enrolled low-risk pregnancy subjects aged ≥18 years from the obstetrics and gynecology clinic of the University of Utah Hospital.

Methods

Maternal macular, skin, and serum carotenoid concentrations were measured using autofluorescence imaging, resonance Raman spectroscopy, and high-performance liquid chromatography, respectively. Infants’ ocular carotenoids and retinal architecture were measured by blue light reflectance imaging and spectral-domain OCT, respectively.

Main Outcome Measures

Changes in maternal and infant macular pigment, skin, and serum carotenoid status over the study period. Differences in infants’ retinal maturity indicators between the 2 study groups.

Results

Following supplementation, there was a statistically significant increase in maternal macular pigment optical volume (P < 0.001) in the Carotenoid Group relative to the Control Group at all study time points, and there was no detectable maternal ocular carotenoid depletion. Infant skin and serum carotenoids increased significantly in the Carotenoid Group compared with the Control Group. As exploratory endpoints, infants in the Carotenoid Group had a 20% increase in macular pigment optical density (P = 0.242) and more mature foveal parameters compared with those in the Control Group.

Conclusion

Prenatal carotenoid supplementation significantly increased maternal and infant systemic carotenoids and caused a pattern of increased infant ocular carotenoid status, which may benefit both mothers and their infants’ ocular development and function. This study provides important data to design and power a future multicenter study of prenatal carotenoid supplementation in higher-risk pregnancies.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective

Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models. However, whether particular metabolites causally affect the disease has yet to be established.

Design

A 3-tiered analysis of blood metabolites in the United Kingdom (UK) Biobank cohort to identify metabolites that differ in AMD patients with evidence for a putatively causal role in AMD.

Participants

A total of 72 376 donors from the UK Biobank cohort including participants with AMD (N = 1353) and non-AMD controls (N = 71 023).

Methods

We analyzed 325 directly measured or derived blood metabolites from the UK Biobank for 72 376 donors to identify AMD-associated metabolites. Genome-wide association studies for 325 metabolites in 98 316 European participants from the UK Biobank were performed. The causal effects of these metabolites in AMD were tested using a 2-sample Mendelian randomization approach. The predictive value of these measurements together with sex and age was assessed by developing a machine learning classifier.

Main Outcome Measures

Evaluating metabolic biomarkers associated with AMD susceptibility and investigating their potential causal contribution to the development of the disease.

Results

This study noted age to be the prominent risk factor associated with AMD development. While accounting for age and sex, we identified 84 metabolic markers as significantly (false discovery rate-adjusted P value < 0.05) associated with AMD. Lipoprotein subclasses comprised the majority of the AMD-associated metabolites (39%) followed by several lipoprotein to lipid ratios. Nineteen metabolites showed a likely causative role in AMD etiology. Of these, 6 lipoproteins contain very small, very low-density lipoprotein (VLDL), and phospholipids to total lipid ratio in medium VLDL. Based on this we postulate that depletion of circulating very small VLDLs is likely causal for AMD. The risk prediction model constructed from the metabolites, age and sex, identified age as the primary predictive factor with a much smaller contribution by metabolites to AMD risk prediction.

Conclusions

This study underscores the pronounced role of lipids in AMD susceptibility and the likely causal contribution of particular subclasses of lipoproteins to AMD. Our study provides valuable insights into the metabopathological mechanisms of AMD disease development and progression.

Objective

In this study, we aimed to evaluate cellular alterations in the foveal neuroglia of eyes with idiopathic epiretinal membrane (ERM) and examine their correlation with visual function. We also aimed to identify prognostic markers for visual outcomes postvitrectomy.

Design

A prospective longitudinal study.

Subjects

The study comprised 84 subjects, including 50 eyes diagnosed with idiopathic ERM and 34 healthy eyes serving as controls.

Methods

The foveal neuroglial changes in eyes with idiopathic ERM were determined using adaptive optics OCT (AO-OCT) by comparing them with healthy eyes. For patients with ERM, the ERM and inner limiting membrane were removed during vitrectomy in all eyes.

Main Outcome Measures

Foveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) and M-CHARTS scores, evaluated preoperatively and at 1, 3, and 6 months postoperatively, and associations between foveal neuroglial changes and these parameters.

Results

Adaptive optics OCT revealed discernible differences in the foveal cones of the eyes with ERM and their healthy counterparts. The thickness of the ellipsoid zone (EZ) band was augmented in eyes with ERM. The alignment of the Müller cells was more vertical and the density of the foveal cone cell nuclei was higher in eyes with ERM than in healthy eyes. Within the AO-OCT parameters, the higher cone nuclei count correlated with worse M-CHARTS scores, both preoperatively and 6 months postoperatively (P = 0.004, 0.010, respectively). Greater EZ thickness was significantly associated with poorer 6-month postoperative BCVA (P = 0.005).

Conclusions

Adaptive optics OCT can be used to precisely identify cellular alterations in eyes with ERM that are closely related to visual function impairments. These cellular insights enhance our understanding of ERM pathology and offer promising prognostic indicators of visual outcome after vitrectomy.

Vision is the most powerful sense guiding our interaction with the environment. Its process starts with the retinal image as input and results in visually guided behaviors as output. This paper summarizes insights I gained over >40 years dealing with clinical ophthalmology, visual science, and vision rehabilitation, disciplines that all involve vision, but from different points of view. The retinal image contains 2-dimensional forms that have no inherent meaning. The brain matches this input to stored concepts, to create a Mental Model that is filled with 3-dimensional objects that are meaningful and linked to other senses. Ultimately this leads to the output of goal-directed visually guided behavior. The processes involved are too complex to be covered by a single practitioner. Optimal vision rehabilitation requires teamwork that includes contributions from various professions. It also requires an understanding, as well as possible, of the cerebral processes involved. The visual sciences study mostly the input-driven process from retinal image to visual percepts. Their studies deal mostly with groups and group averages and only occasionally with individual disease conditions. Clinical ophthalmology deals mostly with individuals, rather than group averages. The motto of the American Academy of Ophthalmology reminds us that the end point of patient care goes beyond “preserving sight.” It also includes “empowering lives” by creating the conditions for goal-directed interaction with the environment through visually directed behavior. Traditionally, the study of vision has mainly involved the conscious part of vision, handled mostly in the ventral stream. However, the subconscious part of vision, handled mostly in the dorsal stream must also be considered. This is further stimulated by the demands of computer vision, image processing, and artificial intelligence. Vision rehabilitation traditionally deals with the input side through better illumination and various magnification devices. This is the domain of low vision aids. Increasingly, however, it must also address the output side, and the involvement of other senses (braille, long cane, and talking books). This requires better understanding of the goal-directed higher visual processes. The supplemental material covers the development of numerical scales to quantify not only visual acuity but also visual abilities, and the use of different tests.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective

To characterize the effect of netarsudil 0.02% on episcleral blood flow in treatment-naive glaucoma suspect or ocular hypertension subjects.

Design

Prospective, unmasked, single-arm cohort study.

Participants

Ten treatment-naive patients with a diagnosis of glaucoma suspect or ocular hypertension.

Methods

Erythrocyte-mediated angiography (EMA) was used to measure episcleral erythrocyte velocity, vessel diameter, and blood flow at baseline before treatment, 1 hour after drop instillation (T1), 1 to 2 weeks after daily netarsudil 0.02% drop use (T2), and 1 hour after drop instillation at the 1-to-2-week time point (T3). Intraocular pressure (IOP) and blood pressure were measured at each visit.

Main Outcome Measures

Change in episcleral venous erythrocyte velocity, diameter, and blood flow between time points analyzed using generalized estimating equation models.

Results

Of the 18 eligible study eyes of 10 enrolled treatment-naive subjects, baseline IOP was 16.8 ± 3.6 mmHg (mean ± standard deviation), which significantly decreased to 13.9 ± 4.2 mmHg at T1, 12.6 ± 4.1 mmHg at T2, and 11.8 ± 4.7 mmHg at T3 (P < 0.05 at each time point compared with baseline). Episcleral vessels averaged 61.3 ± 5.3 μm in diameter at baseline which increased significantly at all posttreatment time points (78.0 ± 6.6, 74.0 ± 5.2, 76.9 ± 6.9 μm, respectively; mean ± standard deviation, P < 0.05 for each time point). Episcleral venous flowrates were 0.40 ± 0.22 uL/minute (mean ± standard deviation) at baseline, which increased significantly to 0.69 ± 0.45 uL/min at T1 (P = 0.01), did not significantly differ at T2 (0.38 ± 0.30 uL/minute), and increased significantly to 0.54 ± 0.32 uL/minute at T3 (P < 0.05 compared with baseline and T2).

Conclusions

Netarsudil causes episcleral venous dilation at all time points and resulting increases in episcleral venous flowrates 1 hour after drop instillation. Increased episcleral venous flow, associated with decreased episcleral venous pressure, may result in lowered IOP.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose

To test the use of a virtual reality visual field headset (VRVF) for implementation of the Esterman visual field (EVF) test as compared with standard automated perimetry (SAP) among people with glaucoma.

Design

Experimental design.

Subjects

Patients with mild to severe glaucoma ranging from 10 to 90 years who presented for follow-up at a glaucoma clinic in Miami, Florida were eligible.

Methods

Participants performed the EVF test on both SAP and VRVF. Five glaucoma-trained ophthalmologists were then asked to rate all anonymized SAP and RVF tests as a “pass” or “failure” based on Florida state law.

Main Outcome Measures

Point-by-point concordance between original VRVF EVF test results and SAP EVF test results was calculated using the Kappa statistic. Concordance between SAP and VRVF was secondarily assessed with a conditional logistic regression based on the pass-failure determinations by the glaucoma-trained ophthalmologists. Interrater agreement on test pass-failure determinations was also calculated. Finally, test results on SAP versus VRVF were compared based on Esterman efficiency score (EES), the number of correct points divided by the number of total points, and duration of testing.

Results

Twenty-two subjects were included in the study with ages ranging from 14 to 78 years old. Concordance between VRVF and SAP test using point-by-point analysis was poor (κ = 0.332, [95% confidence intervals {CI}: 0.157, 0.506]) and somewhat increased using pass-failure determinations from ophthalmologists (κ = 0.657, [95% CI: 0.549, 0.751]). Ophthalmologists were more likely to agree amongst themselves on pass-failure determinations for VRVF tests (κ = 0.890, [95% CI: 0.726, 0.964]) than for SAP (κ = 0.590, [95% CI: 0.372, 0.818]); however, VRVF demonstrated significantly lower EES than SAP (median EES difference: 4.5 points, P = 0.021).

Conclusions

This pilot study is the first to assess the implementation of the EVF test using a virtual reality headset. Based on the weak overall agreement between VRVF and SAP, the current VRVF EVF test is not an acceptable determinant of driver’s licensing. However, ophthalmologists were more likely to agree amongst themselves on VRVF test reports than on SAP reports. With further testing and improvement, virtual reality may eventually become a portable and convenient method for administering the EVF test.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose

Circulating tumor DNA (ctDNA) is released into the plasma by many cancers and offers clinical applications including noninvasive diagnostics. Histiocytosis results from myelogenous clonal expansion of histiocytes, predominantly driven by mutations in the mitogen-activated protein kinase pathway that are potentially detectable by ctDNA-based sequencing assays. However, ocular-involving histiocytosis is often a diagnostic challenge leading to delayed diagnosis and the need for invasive biopsy of sensitive ocular structures. The purpose of this study is to determine whether sequencing of plasma-derived ctDNA can noninvasively diagnose ocular-involving histiocytosis.

Design

Single tertiary cancer referral center.

Participants

Twenty-four adult patients with ocular-involving histiocytosis and ctDNA sequencing.

Methods

Circulating tumor DNA was analyzed (via digital droplet polymerase chain reaction for BRAF V600E, and/or next-generation sequencing) and variant allele frequency was measured at initial presentation to our center. Patient demographics, clinical characteristics, and oncogenic mutations identified from tumor-based sequencing were recorded.

Main Outcome Measures

Plasma-derived ctDNA detectability of pertinent driver mutations of histiocytosis.

Results

At the initial presentation of 14 patients with ocular-involving histiocytosis, sequencing of plasma-derived ctDNA detected driver mutations for histiocytosis (BRAF V600E [10], KRAS [2], ARAF [1], and concurrent MAP2K1/KRAS [1]). Mutations found in circulating cell-free DNA were 100% concordant in 11 of 11 patients with mutations identified by solid tumor sequencing. Of 10 patients without driver mutation detected in ctDNA, 3 patients had alterations (CBL mutation or kinase fusion) not captured in the ctDNA sequencing assay, 3 were wildtype even by tumor sequencing; in 4 patients, tumor-based sequencing identified mutations (BRAF [2], MAP2K1 [2]) not detected in ctDNA. Detectable mutations in ctDNA were significantly more likely in patients with uveal infiltration (P = 0.036).

Conclusions

In this cohort, plasma-derived ctDNA was detectable and diagnostic in the majority of patients with ocular-involving histiocytosis. This suggests that if ocular histiocytosis is suspected (particularly if involving the uvea), noninvasive plasma-derived ctDNA analysis is a helpful diagnostic tool that may obviate the need to invasively biopsy sensitive ocular structures.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Objective

Training data fuel and shape the development of artificial intelligence (AI) models. Intensive data requirements are a major bottleneck limiting the success of AI tools in sectors with inherently scarce data. In health care, training data are difficult to curate, triggering growing concerns that the current lack of access to health care by under-privileged social groups will translate into future bias in health care AIs. In this report, we developed an autoencoder to grow and enhance inherently scarce datasets to alleviate our dependence on big data.

Design

Computational study with open-source data.

Subjects

The data were obtained from 6 open-source datasets comprising patients aged 40–80 years in Singapore, China, India, and Spain.

Methods

The reported framework generates synthetic images based on real-world patient imaging data. As a test case, we used autoencoder to expand publicly available training sets of optic disc photos, and evaluated the ability of the resultant datasets to train AI models in the detection of glaucomatous optic neuropathy.

Main Outcome Measures

Area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the glaucoma detector. A higher AUC indicates better detection performance.

Results

Results show that enhancing datasets with synthetic images generated by autoencoder led to superior training sets that improved the performance of AI models.

Conclusions

Our findings here help address the increasingly untenable data volume and quality requirements for AI model development and have implications beyond health care, toward empowering AI adoption for all similarly data-challenged fields.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose

To use artificial intelligence to identify imaging biomarkers for anatomic and functional progression of lamellar macular hole (LMH) and elaborate a deep learning (DL) model based on OCT and OCT angiography (OCTA) for prediction of visual acuity (VA) loss in untreated LMHs.

Design

Multicentric retrospective observational study.

Participants

Patients aged >18 years diagnosed with idiopathic LMHs with availability of good quality OCT and OCTA acquisitions at baseline and a follow-up >2 years were recruited.

Methods

A DL model based on soft voting of 2 separate models (OCT and OCTA-based respectively) was trained for identification of cases with VA loss >5 ETDRS letters (attributable to LMH progression only) during a 2-year follow-up. Biomarkers of anatomic and functional progression of LMH were evaluated with regression analysis, feature learning (support vector machine [SVM] model), and visualization maps.

Main Outcome Measures

Ellipsoid zone (EZ) damage, volumetric tissue loss (TL), vitreopapillary adhesion (VPA), epiretinal proliferation, central macular thickness (CMT), parafoveal vessel density (VD) and vessel length density (VLD) of retinal capillary plexuses, choriocapillaris (CC), and flow deficit density (FDD).

Results

Functionally progressing LMHs (VA-PROG group, 41/139 eyes [29.5%]) showed higher prevalence of EZ damage, higher volumetric TL, higher prevalence of VPA, lower superficial capillary plexus (SCP), VD and VLD, and higher CC FDD compared with functionally stable LMHs (VA-STABLE group, 98/139 eyes [70.5%]). The DL and SVM models showed 92.5% and 90.5% accuracy, respectively. The best-performing features in the SVM were EZ damage, TL, CC FDD, and parafoveal SCP VD. Epiretinal proliferation and lower CMT were risk factors for anatomic progression only.

Conclusions

Deep learning can accurately predict functional progression of untreated LMHs over 2 years. The use of AI might improve our understanding of the natural course of retinal diseases. The integrity of CC and SCP might play an important role in the progression of LMHs.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose

To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA).

Design

Retrospective, multicenter, observational study.

Participants

A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group.

Methods

The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype.

Main Outcome Measures

Clinical characteristics and progression rates of pachychoroid and conventional GA.

Results

The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 μm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm^2; P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001).

Conclusions

Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.