Using optical coherence tomography and optical coherence tomography angiography to delineate neurovascular homeostasis in migraine: a review.

Migraine is one of the world's most debilitating disorders, and it has recently been shown that changes in the retina can be a potential biomarker for the disease. These changes can be detected by optical coherence tomography (OCT), which measures retinal thickness, and optical coherence tomography angiography (OCTA), which measures vessel density. We searched the databases Google Scholar, ProQuest, Scopus, and Web of Science for studies in English using OCT and OCTA in migraineurs, using the search terms "optical coherence tomography," "OCT," "optical coherence tomography angiography," "OCTA" and "migraine." We found 73 primary studies, 11 reviews, and 8 meta-analyses pertaining to OCT and OCTA findings in migraineurs. They showed that migraineurs had reduced retinal thickness (via OCT), retinal vessel density, and greater foveal avascular zone area (via OCTA) than controls. OCTA changes reflect a perfusion compromise occurring in migraineurs as opposed to in healthy controls. OCT and OCTA deficits were worse in migraine-with-aura and chronic migraine than in migraine-without-aura and episodic migraine. Certain areas of the eye, such as the fovea, may be more vulnerable to these perfusion changes than other parts. Direct comparison between study findings is difficult because of the heterogeneity between the studies in terms of both methodology and analysis. Moreover, as almost all case-control studies were cross-sectional, more longitudinal cohort studies are needed to determine cause and effect between migraine pathophysiology and OCT/OCTA findings. Current evidence suggests both OCT and OCTA may serve as retinal markers for migraineurs, and further research in this field will hopefully enable us to better understand the vascular changes associated with migraine, perhaps also providing a new diagnostic and therapeutic biomarker.

Nonlinear Reduction in Hyperautofluorescent Ring Area in Retinitis Pigmentosa.

PURPOSE: To report baseline dimension of the autofluorescent (AF) ring in a large cohort of retinitis pigmentosa (RP) patients and to evaluate models of ring progression. DESIGN: Cohort study. PARTICIPANTS: Four hundred and forty-five eyes of 224 patients with clinical diagnosis of RP. METHODS: Autofluorescent rings from near-infrared AF (NIRAF) and short-wavelength AF (SWAF) imaging modalities in RP eyes were segmented with ring area and horizontal extent extracted from each image for cross-sectional and longitudinal analyses. In longitudinal analysis, for each eye, ring area, horizontal extent, and natural logarithm of the ring area were assessed as the best dependent variable for linear regression by evaluating R2 values. Linear mixed-effects modeling was utilized to account for intereye correlation. MAIN OUTCOME MEASURES: Autofluorescent ring size characteristics at baseline and ring progression rates. RESULTS: A total of 439 eyes had SWAF imaging at baseline with the AF ring observed in 206 (46.9%) eyes. Mean (95% confidence interval) of ring area and horizontal extent were 7.85 (6.60 to 9.11) mm2 and 3.35 (3.10 to 3.60) mm, respectively. In NIRAF, the mean ring area and horizontal extent were 7.74 (6.60 to 8.89) mm2 and 3.26 (3.02 to 3.50) mm, respectively in 251 out of 432 eyes. Longitudinal analysis showed mean progression rates of -0.57 mm2/year and -0.12 mm/year in SWAF using area and horizontal extent as the dependent variable, respectively. When ln(Area) was analyzed as the dependent variable, mean progression was -0.07 ln(mm2)/year, which equated to 6.80% decrease in ring area per year. Similar rates were found in NIRAF (area: -0.59 mm2/year, horizontal extent: -0.12 mm/year and ln(Area): -0.08 ln(mm2)/year, equated to 7.75% decrease in area per year). Analysis of R2 showed that the dependent variable ln(Area) provided the best linear model for ring progression in both imaging modalities, especially in eyes with large overall area change. CONCLUSIONS: Our data suggest that using an exponential model to estimate progression of the AF ring area in RP is more appropriate than the models assuming linear decrease. Hence, the progression estimates provided in this study should provide more accurate reference points in designing clinical trials in RP patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Distribution of Axial Length in Australians of Different Age Groups, Ethnicities, and Refractive Errors.

Purpose: Treatments are available to slow myopic axial elongation. Understanding normal axial length (AL) distributions will assist clinicians in choosing appropriate treatment for myopia. We report the distribution of AL in Australians of different age groups and refractive errors. Methods: Retrospectively collected spherical equivalent refraction (SER) and AL data of 5938 individuals aged 5 to 89 years from 8 Australian studies were included. Based on the SER, participants were classified as emmetropes, myopes, and hyperopes. Two regression model parameterizations (piece-wise and restricted cubic splines [RCS]) were applied to the cross-sectional data to analyze the association between age and AL. These results were compared with longitudinal data from the Raine Study where the AL was measured at age 20 (baseline) and 28 years. Results: A piece-wise regression model (with 1 knot) showed that myopes had a greater increase in AL before 18 years by 0.119 mm/year (P < 0.001) and after 18 years by 0.011 mm/year (P < 0.001) compared to emmetropes and hyperopes, with the RCS model (with 3 knots) showing similar results. The longitudinal data from the Raine Study revealed that, when compared to emmetropes, only myopes showed a significant change in the AL in young adulthood (by 0.016 mm/year, P < 0.001). Conclusions: The AL of myopic eyes increases more rapidly in childhood and slightly in early adulthood. Further studies of longitudinal changes in AL, particularly in childhood, are required to guide myopia interventions. Translational Relevance: The axial length of myopic eyes increases rapidly in childhood, and there is a minimal increase in the axial length in non-myopic eyes after 18 years of age.

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration.

BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

L-arginine and aged garlic extract for the prevention of migraine: a study protocol for a randomised, double-blind, placebo-controlled, phase-II trial (LARGE trial).

BACKGROUND: Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines. METHODS: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention. DISCUSSION: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated. TRIAL REGISTRATION: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.

Microperimetry and Adaptive Optics Imaging Reveal Localized Functional and Structural Changes in Asymptomatic RPGR Mutation Carriers.

Purpose: Female carriers of RPGR mutations demonstrate no significant retinal dysfunction or structural change despite a characteristic tapetal-like reflex. In this study, we examined localized changes of pointwise sensitivity (PWS) and cone density (CD) using microperimetry (MP) and adaptive optics (AO) imaging in female carriers of RPGR mutations. Methods: In this cross-sectional case-control study, MP (MAIA, 10-2 test grid) and AO imaging (rtx1) were performed in female carriers of RPGR mutations and unrelated age-matched healthy controls. PWS at 68 loci located 1 degree to 9 degrees away from the preferred retinal locus and CD at 12 loci located 1 degree to 3 degrees away from the foveal center were measured. Severity of defect was defined by standard deviation (SD) from age-matched healthy control means: normal (<1 SD from normal average), moderate defect (1-2 SD from normal average), and severe defect (>2 SD from normal average). Results: Twelve patients from seven unrelated families were enrolled. Seven patients were asymptomatic, 5 of whom had visual acuity 20/20 or better in both eyes. PWS and CD were available in 12 and 8 patients, respectively. Severe PWS and CD defect in at least 1 test location was observed in 10 of 12 patients and 7 of 8 patients, respectively. Among the five asymptomatic patients who had normal visual acuity, severe PWS and CD defects were observed in three of five and four of five patients, respectively. Conclusions: MP and AO imaging revealed early functional and structural changes in asymptomatic RPGR mutation carriers and should be considered in clinical assessment of these patients.

Conjunctival ultraviolet autofluorescence area decreases with age and sunglasses use.

BACKGROUND: Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting conjunctival damage related to ultraviolet radiation exposure. In cross-sectional studies, CUVAF area is positively associated with self-reported time spent outdoors and pterygium and negatively associated with myopia; however, longitudinal studies are scarce. AIMS: To use a novel deep learning-based tool to assess 8-year change in CUVAF area in young adults, investigate factors associated with this change and identify the number of new onset pterygia. METHODS: A deep learning-based CUVAF tool was developed to measure CUVAF area. CUVAF area and pterygium status were assessed at three study visits: baseline (participants were approximately 20 years old) and at 7-year and 8-year follow-ups. Participants self-reported sun protection behaviours and ocular history. RESULTS: CUVAF data were available for 1497 participants from at least one study visit; 633 (43%) participants had complete CUVAF data. Mean CUVAF areas at baseline and the 7-year and 8-year follow-ups were 48.4, 39.3 and 37.7 mm2, respectively. There was a decrease in mean CUVAF area over time (change in total CUVAF area=-0.96 mm2 per year (95% CI: -1.07 to -0.86)). For participants who wore sunglasses ≥1/2 of the time, CUVAF area decreased by an additional -0.42 mm2 per year (95% CI: -0.72 to -0.12) on average. Fourteen (1.5%) participants developed a pterygium. CONCLUSIONS: In this young adult cohort, CUVAF area declined over an 8-year period. Wearing sunglasses was associated with a faster reduction in CUVAF area. Deep learning-based models can assist in accurate and efficient measurement of CUVAF area.

Deep learning: applications in retinal and optic nerve diseases.

Deep learning (DL) represents a paradigm-shifting, burgeoning field of research with emerging clinical applications in optometry. Unlike traditional programming, which relies on human-set specific rules, DL works by exposing the algorithm to a large amount of annotated data and allowing the software to develop its own set of rules (i.e. learn) by adjusting the parameters inside the model (network) during a training process in order to complete the task on its own. One major limitation of traditional programming is that, with complex tasks, it may require an extensive set of rules to accurately complete the assignment. Additionally, traditional programming can be susceptible to human bias from programmer experience. With the dramatic increase in the amount and the complexity of clinical data, DL has been utilised to automate data analysis and thus to assist clinicians in patient management. This review will present the latest advances in DL, for managing posterior eye diseases as well as DL-based solutions for patients with vision loss.

Evaluating Distribution of Foveal Avascular Zone Parameters Corrected by Lateral Magnification and Their Associations with Retinal Thickness.

Purpose: To examine the distribution of foveal avascular zone (FAZ) parameters, with and without correction for lateral magnification, in a large cohort of healthy young adults. Design: Cross-sectional, observational cohort study. Participants: A total of 504 healthy adults, 27 to 30 years of age. Methods: Participants underwent a comprehensive ophthalmic examination including axial length measurement and OCT angiography (OCTA) imaging of the macula. OCT angiography images of combined superficial and deep retinal vessel plexuses were processed via a custom software to extract foveal avascular zone area (FAZA) and foveal density-300 (FD-300), the vessel density in a 300-µm wide annulus surrounding the FAZ, with and without correction for lateral magnification. Bland-Altman analyses were performed to examine the effect of lateral magnification on FAZA and FD-300, as well as to evaluate the interocular agreement in both parameters. Linear mixed-effects models were used to examine the relationship between retinal thicknesses and OCTA parameters. Main Outcome Measures: The FAZA and FD-300, corrected for lateral magnification. Results: The mean (standard deviation [SD]) of laterally corrected FAZA and FD-300 was 0.22 mm2 (0.10 mm2) and 51.9% (3.2%), respectively. Relative to uncorrected data, 55.6% of corrected FAZA showed a relative change > 5%, whereas all FD-300 changes were within 5%. There was good interocular symmetry (mean right eye-left eye difference, 95% limits of agreement [LoA]) in both FAZA (0.006 mm2, -0.05 mm2, to 0.07 mm2) and FD-300 (-0.05%, -5.39%, to 5.30%). There were significant negative associations between central retinal thickness and FAZA (ß = -0.0029), as well as between central retinal thickness and FD-300 (ß = -0.044), with the relationships driven by inner, not outer, retina. Conclusions: We reported lateral magnification adjusted normative values for FAZA and FD-300 in a large cohort of young, healthy eyes. Clinicians should strongly consider accounting for lateral magnification when evaluating FAZA. Good interocular agreement in FAZA and FD-300 suggests the contralateral eye can be used as control data.

Correcting magnification error in foveal avascular zone area measurements of optical coherence tomography angiography images with estimated axial length.

BACKGROUND: To generate and validate a method to estimate axial length estimated (ALest) from spherical equivalent (SE) and corneal curvature [keratometry (K)], and to determine if this ALest can replace actual axial length (ALact) for correcting transverse magnification error in optical coherence tomography angiography (OCTA) images using the Littmann-Bennett formula. METHODS: Data from 1301 participants of the Raine Study Gen2-20 year follow-up were divided into two datasets to generate (n = 650) and validate (n = 651) a relationship between AL, SE, and K. The developed formula was then applied to a separate dataset of 46 participants with AL, SE, and K measurements and OCTA images to estimate and compare the performance of ALest against ALact in correcting transverse magnification error in OCTA images when measuring the foveal avascular zone area (FAZA). RESULTS: The formula for ALest yielded the equation: ALest = 2.102K - 0.4125SE + 7.268, R2 = 0.794. There was good agreement between ALest and ALact for both study cohorts. The mean difference [standard deviation (SD)] between FAZA corrected with ALest and ALact was 0.002 (0.015) mm2 with the 95% limits of agreement (LoA) of - 0.027 to 0.031 mm2. In comparison, mean difference (SD) between FAZA uncorrected and corrected with ALact was - 0.005 (0.030) mm2, with 95% LoA of - 0.064 to 0.054 mm2. CONCLUSIONS: ALact is more accurate than ALest and hence should be used preferentially in magnification error correction in the clinical setting. FAZA corrected with ALest is comparable to FAZA corrected with ALact, while FAZA measurements using images corrected with ALest have a greater accuracy than measurements on uncorrected images. Hence, in the absence of ALact, clinicians should use ALest to correct for magnification error as this provides for more accurate measurements of fundus parameters than uncorrected images.

Association between dietary niacin and retinal nerve fibre layer thickness in healthy eyes of different ages.

BACKGROUND: To investigate the relationship between dietary intake of niacin (water-soluble form of vitamin B3 ) and retinal nerve fibre layer (RNFL) thickness in healthy eyes. METHODS: This cross-sectional study examined the association between daily niacin intake and RNFL thickness in three large population-based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data; energy-adjusted niacin intake was estimated from food frequency questionnaires. Linear mixed-effects models were utilised to examine the association between RNFL thickness and energy-adjusted niacin intake. Three separate analyses were conducted, with niacin treated as a continuous, a categorical (quartiles) or a dichotomous (above/below Australian recommended daily intake) variable. RESULTS: In total, 4937 subjects were included in the study [Raine Study Gen2, n = 1204, median age 20; Busselton Healthy Ageing Study (BHAS), n = 1791, median age 64; TwinsUK, n = 1942, median age 64). When analysed as a continuous variable, there was no association between RNFL thickness and niacin intake in any of the three cohorts (95% CI ß: Raine Study Gen 2, -0.174 to 0.074; BHAS, -0.066 to 0.078; TwinsUK -0.435 to 0.350). Similar findings were observed with quartiles of niacin intake and for niacin intakes above or below Australian recommended daily intake levels in all three cohorts. CONCLUSIONS: Dietary intake of niacin from a standard diet does not appear to be associated with age-related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina.

Prevalence of Toxoplasmic Retinochoroiditis in an Australian Adult Population: A Community-Based Study.

PURPOSE: Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50% of the human population is estimated to be infected with T. gondii; however, the epidemiology of toxoplasmic retinochoroiditis has not been widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data that were collected as part of the Busselton Healthy Ageing Study. DESIGN: Cross-sectional, community-based, prospective cohort study. PARTICIPANTS: 5020 Australian adults (2264 men and 2756 women; age range, 45-69 years, and median age, 58 years). METHODS: Retinal color photographs, centered on the optic disc and macula, were captured using a digital retinal camera after the dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis. MAIN OUTCOME MEASURES: Prevalence of toxoplasmic retinochoroiditis. RESULTS: Eight participants (0.16%) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81% of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021;11:3420), the prevalence of toxoplasmic retinochoroiditis was estimated to be 0.67% or 1 per 149 persons. CONCLUSIONS: Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified.

Localised relative scotoma in cuticular drusen.

PURPOSE: To investigate retinal sensitivity changes in eyes with pure cuticular drusen. METHODS: Multimodal imaging and microperimetry (37-loci grid) data were examined retrospectively to evaluate functional changes in eyes with pure cuticular drusen. Mean sensitivity in the cuticular drusen cohort was compared to age-matched normals. An age- and loci-specific normative reference was created to analyse localised sensitivity deviation. RESULTS: The mean number loci with relative scotoma in the cuticular drusen cohort (n = 27, mean [SD] age: 48.5 [12.4] years) referenced to normal eyes (n = 80, 53.5 [14.6] years) was 5.5 (95% confidence interval 3.0 to 8.1). However, mean sensitivity was not statistically different to the age-matched normal cohort (95% CI, - 2.3 to + 3.4 dB). The 37-loci grid was stratified into three rings of the approximately same number of loci, and the percentage of cuticular drusen eyes with pointwise deviation was significantly lower in the inner compared to the middle ring (12.3 [5.3]% vs. 17.3 [5.1]%, p < 0.05). CONCLUSIONS: Eyes with cuticular drusen demonstrated relative scotoma, but mean sensitivity was not affected. Pointwise sensitivity provides a more robust measure of retinal sensitivity than mean sensitivity in cuticular drusen and should be assessed both in the clinic and in future clinical trials.

Short-Term Parafoveal Cone Loss Despite Preserved Ellipsoid Zone in Rod Cone Dystrophy.

Purpose: Rod-cone dystrophy (RCD) is characterized by centripetal loss of rod followed by cone photoreceptors. In this prospective, observational cohort, we used flood-illumination adaptive optics (AO) imaging to investigate parafoveal cone loss in regions with preserved ellipsoid zone (EZ) in patients with RCD. Methods: Eight patients with RCD and 10 age-matched healthy controls underwent spectral-domain optical coherence tomography and AO imaging. The RCD cohort underwent a follow-up examination after 6 months. Cone density (CD) and intercone distance (ICD) measurements were performed at 2° temporal from the fovea. Baseline CD and ICD values were compared between the control and patient groups, and longitudinal changes were calculated in the patient group. Residual EZ span in patients was measured in horizontal foveal B-scans. Results: Between the control and patient groups, there was no significant difference in the baseline CD (2094 vs. 1750 cells/deg2, respectively; P = 0.09) and ICD (1.46 vs. 1.62 arcmin, respectively; P = 0.08). Mean CD declined by 198 cells/deg2 (-11.3%; P < 0.01), and mean ICD increased by 0.09 arcmin (+5.6%; P = 0.01) at the 6-month follow-up in the patient group. Mean baseline and follow-up residual EZ spans in the six patients with EZ defect were 3189 µm and 3065 µm, respectively (-3.9%; P = 0.08). Conclusions: AO imaging detected significant parafoveal cone loss over 6-month follow-up even in regions with preserved EZ. Further studies to refine AO imaging protocol and validate cone metrics as a structural endpoint in early RCD are warranted. Translational Relevance: CD and ICD may change prior to EZ span shortening in RCD.

Correction: Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

[This corrects the article DOI: 10.1371/journal.pgen.1009497.].

Distribution and Classification of Peripapillary Retinal Nerve Fiber Layer Thickness in Healthy Young Adults.

Purpose: To report the distribution of peripapillary retinal nerve fiber layer (RNFL) thickness in healthy young adults, investigate factors associated with RNFL thickness, and report the percentage of outside normal limits (ONL) and borderline (BL) RNFL thickness classifications based on the optical coherence tomography (OCT) manufacturer reference database. Methods: Participants of the Raine Study Generation 2 cohort (aged 18-22 years) underwent spectral domain OCT imaging with an RNFL circle scan. Eyes with inadequate scans or optic nerve pathology were excluded. Linear mixed models were used to analyze associations. Results: Data were available for 1288 participants (mean age, 20.0 years). Mean RNFL thicknesses in right and left eyes, respectively, were global = 100.5 µm, 100.3 µm (P = 0.03); temporal = 73.1 µm, 68.9 µm (P < 0.001); superotemporal = 140.6 µm, 136.3 µm (P < 0.001); superonasal = 104.9 µm, 115.1 µm (P < 0.001); nasal = 79.7 µm, 79.1 µm (P = 0.09); inferonasal = 109.8 µm, 111.5 µm (P < 0.001); and inferotemporal = 143.2 µm, 143.6 µm (P = 0.51). Longer axial length was associated with thinner RNFL globally, nasally, inferotemporally, superotemporally, superonasally, and inferonasally, as well as thicker RNFL temporally. The prevalence of ONL and BL classifications was generally higher than the expected rates of 1% and 4%, respectively, in temporal sectors and lower than expected in nasal sectors. The prevalence of global BL classifications was lower than expected (right eye, 2.3%; left eye, 2.6%). Conclusions: Measured RNFL thickness differs with axial length and between right and left eyes. More reference data are needed to better define the normal limits of RNFL variation in different populations. Translational Relevance: This study provides an improved understanding of normal variation in RNFL thickness in young adults.

Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.

Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor receptor 1-3 tyrosine kinase inhibitor anticancer therapy.

BACKGROUND: To describe ocular adverse events and retinal changes during fibroblast growth factor receptor (FGFR) inhibitor (AZD4547) anticancer therapy. METHODS: This is a sub-study examining ocular adverse effects from AZD4547 therapy (single-centre, open-label, single arm phase II clinical trial). Comprehensive ocular examinations were performed 3 weekly in 24 patients. Macular optical coherence tomography (OCT) scan (300 × 250 ) was obtained at each visit and OCT parameters [central 1 mm retinal thickness (CRT) and total macular volume in central 6 mm] extracted. OCT scans were subdivided into outer (ELM to RPE) and inner (ELM to ILM) layers to compare outer and inner retinal changes. RESULTS: In 24 patients, AZD4547 was associated with eyelash elongation (n = 5, 21%) and punctate corneal erosion (n = 2, 8%). One patient developed clinically significant posterior capsular opacification during the study. OCT data were available in 23 patients, retinal changes ranged from an asymptomatic increased visibility of the interdigitation zone (IDZ) (n = 10, 43%) to multilobular subretinal fluid pockets (n = 5, 22%), which was associated with mild visual acuity loss. In a subset of patients (n = 9) with pre-AZD4547 dosing OCT baseline, CRT increased by mean (SD) of 9 (4) µm in those with IDZ change only compared with 64 (38) µm in those with other retinal changes. Retinal changes tended to be bilateral, self-limiting and improved over time without medical intervention. CONCLUSIONS: The ocular signs and symptoms did not result in dose cessation. Posteriorly, FGFR inhibition leads to outer retinal changes ranging from increased visibility of IDZ to distinct, multiple fluid pockets.

Macular Thickness Profile and Its Association With Best-Corrected Visual Acuity in Healthy Young Adults.

Purpose: To describe the thickness profiles of the full retinal and outer retinal layers (ORL) at the macula in healthy young adults, and associations with best-corrected visual acuity (BCVA). Methods: In total, 1604 participants (19-30 years) underwent an eye examination that included measurements of their BCVA, axial length, and autorefraction. The retinal thickness at the foveal pit and at the nine Early Treatment of Diabetic Retinopathy Study macular regions (0.5-mm radius around the fovea, and superior, inferior, temporal, and nasal quadrants of the inner and outer rings of the macula) were obtained using spectral-domain optical coherence tomography imaging. A custom program was used to correct for transverse magnification effects because of different axial lengths. Results: The median full retinal and ORL thicknesses at the central macula were 285 µm and 92 µm. The full retina was thinnest centrally and thickest at the inner macula ring, whereas the ORL was thickest centrally and gradually decreased in thickness with increasing eccentricity. There was no association between axial length and the full retinal or ORL thickness. Increased thicknesses of the full retina at the central macula was associated with better BCVA; however, the effect size was small and not clinically significant. Conclusions: This article mapped the full retinal and ORL thickness profile in a population-based sample of young healthy adults. Translational Relevance: Thickness values presented in this article could be used as a normative reference for future studies on young adults and in clinical practice.