In vivo assessment of cone loss and macular perfusion in children with myopia.

This study evaluated cone density (CD) in the macular region and assess macular perfusion in children with varying degrees of myopia. This was a prospective, cross-sectional, observational study. Children underwent confocal scanning laser ophthalmoscopy (cSLO), optical coherence tomography (OCT), and OCT angiography (OCTA) imaging. A built-in software was used to measure mean CD (cells/mm2), retinal vessel density, choriocapillaris perfusion area, and choroidal thickness (CT). The study included 140 eyes from children categorized into four groups: emmetropia (31 eyes), low myopia (44 eyes), moderate myopia (31 eyes), and high myopia (34 eyes). The high myopia group exhibited significantly lower macular CD than the emmetropia group (P < 0.05). Additionally, the high myopia group showed thinner CT and higher choriocapillaris perfusion area in the macular region than the emmetropia group (all P < 0.01). Macular CD was significantly correlated with age, spherical equivalent, axial length, and CT (all P < 0.05). Generalized linear models revealed CT as the independent factor associated with macular CD (Wald χ2 = 9.265, P = 0.002). Children with high myopia demonstrate reduced CD in the macular region, accompanied by reduced CT. These findings may have important implications for future myopia prevention and management strategies.

Longitudinal In Vivo Imaging of Retinal Cells with Tailored Adeno-Associated Virus Serotypes via Confocal Scanning Laser Ophthalmoscopy.

The dynamic nature of retinal cellular processes necessitates advancements in gene delivery and live monitoring techniques to enhance the understanding and treatment of ocular diseases. This study introduces an optimized adeno-associated virus (AAV) approach, utilizing specific serotypes and promoters to achieve optimal transfection efficiency in targeted retinal cells, including retinal ganglion cells (RGCs) and Müller glia. Leveraging the precision of confocal scanning laser ophthalmoscopy (CSLO), this work presents a non-invasive method for in vivo imaging that captures the longitudinal expression of AAV-mediated green fluorescent protein (GFP). This approach eliminates the need for terminal procedures, preserving the continuity of observation and the well-being of the subject. Furthermore, the GFP signal can be traced in AAV-infected RGCs along the visual pathway to the superior colliculus (SC) and lateral geniculate nucleus (LGN), enabling the potential for direct visual pathway mapping. These findings provide a detailed protocol and demonstrate the application of this powerful tool for real-time studies of retinal cell behavior, disease pathogenesis, and the efficacy of gene therapy interventions, offering valuable insights into the living retina and its connections.

Adaptive optics scanning laser ophthalmoscopy in a heterogenous cohort with Stargardt disease.

Image based cell-specific biomarkers will play an important role in monitoring treatment outcomes of novel therapies in patients with Stargardt (STGD1) disease and may provide information on the exact mechanism of retinal degeneration. This study reports retinal image features from conventional clinical imaging and from corresponding high-resolution imaging with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) in a heterogenous cohort of patients with Stargardt (STGD1) disease. This is a prospective observational study in which 16 participants with clinically and molecularly confirmed STGD1, and 7 healthy controls underwent clinical assessment and confocal AOSLO imaging. Clinical assessment included short-wavelength and near-infrared fundus autofluorescence, spectral-domain optical coherence tomography, and macular microperimetry. AOSLO images were acquired over a range of retinal eccentricities (0°-20°) and mapped to areas of interest from the clinical images. A regular photoreceptor mosaic was identified in areas of normal or near normal retinal structure on clinical images. Where clinical imaging indicated areas of retinal degeneration, the photoreceptor mosaic was disorganised and lacked unambiguous cones. Discrete hyper-reflective foci were identified in 9 participants with STGD1 within areas of retinal degeneration. A continuous RPE cell mosaic at the fovea was identified in one participant with an optical gap phenotype. The clinical heterogeneity observed in STGD1 is reflected in the findings on confocal AOSLO imaging.

Morphology of the normative human cone photoreceptor mosaic and a publicly available adaptive optics montage repository.

Adaptive optics ophthalmoscopy has enabled visualization of the in vivo human photoreceptor mosaic in health, disease and its treatment. Despite this, the clinical utility of the imaging technology has been limited by a lack of automated analysis techniques capable of accurately quantifying photoreceptor structure and a lack of an available normative image database. Here, we present a fully automated algorithm for estimating cone spacing and density over a complete adaptive optics montage along with a database of normative images and cone densities. We imaged the cone mosaics surrounding the fovea and along the horizontal and vertical meridians of fifty normal-sighted controls with a custom-built, multimodal adaptive optics scanning light ophthalmoscope. Cone spacing was automatically measured in the frequency domain and spacing measurements were converted to estimates of cone density at all locations across the montage. Consistent with previous reports, cone density measurements were highest near fovea (152,906 ± 53,209 cones/mm2) and decreased exponentially with eccentricity. A 2.5-fold variation was found in cone density estimates at 0.1 mm, this variation decreased to 1.75-fold at 1 mm. We provide all images, mosaic quantifications, and automated software open source. This database will aid investigators in translating adaptive optics ophthalmoscopy to clinical applications.

Management of Visually Significant Vitreous Opacities.

Visual floaters can significantly affect quality of vision. Although these opacities are visible on ophthalmoscopy, objectively measuring severity has been difficult. The standard approach has been to monitor individuals for complications rather than treating the floaters. With advances in surgical instrumentation and techniques, ophthalmologists have multiple options for treating visually significant floaters, most commonly pars plana vitrectomy and laser vitreolysis. This article aims to review the literature discussing methods for diagnosing and treating floaters.

Longitudinal Imaging of the Foveal Cone Mosaic in CNGA3-Associated Achromatopsia.

Purpose: The purpose of this study was to assess the natural history of the foveal cone mosaic in CNGA3-associated achromatopsia (ACHM). Methods: Thirteen eyes from 10 genetically confirmed patients underwent longitudinal imaging with optical coherence tomography (OCT) and non-confocal split detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans assessed outer nuclear layer (ONL) thickness, foveal ellipsoid zone (EZ) disruption, and foveal hypoplasia. AOSLO images were analyzed to calculate peak foveal cone density (PCD) and mean inter-cell distance (ICD) between cones. Mixed effects models were used to analyze the rate of annual change of PCD and ICD. Results: Mean (±SD) age at visits was 29 ± 10 years, with a follow-up of 2.6 ± 1 years. There was no change in ONL thickness, degree of EZ disruption, or foveal hypoplasia over the follow-up period. We also observed a stable foveal cone mosaic using AOSLO imaging, with no significant change in PCD or ICD. Mean PCD was 15,346 cones/mm² at the mean age of 29 years old (cf. 64,000-324,000 cones/mm² in previously reported healthy controls), with a mean rate of change of -117.79 cones/mm² (0.8%) per year, P = 0.130. Mean ICD at the mean age was 13.82 µm, with a rate of change of 0.17 µm per year, P = 0.83. Conclusions: CNGA3-associated ACHM displays stable foveal cone structure over time with a similar rate of change to CNGB3-associated ACHM (2% decline per year). The stable PCD, small cohort, and large variability within the cohort means significant age associations were not detected.

Multilayer Retinal Correspondence of the Structural and Vascular Anomalies in Eyes With Early Macular Telangiectasia Type 2.

Purpose: To assess the correspondence between interdigitation zone (IZ) reflectivity, ellipsoid zone (EZ) loss, inner retinal layer reflectivity, patterns of capillary dilation, and telangiectasia in eyes with early macular telangiectasia type 2 (MacTel). Patients and Methods: Twenty-eight eyes of 22 patients with grade 0-2 MacTel (according to the MacTel project classification) and 28 healthy control eyes were included in this study. Multimodal imaging, including optical coherence tomography (OCT) angiography, adaptive optics flood illumination ophthalmoscopy (AO-FIO) and blue light reflectance (BLR), was performed. The EZ, IZ, and outer plexiform layer (OPL) were analyzed on the structural OCT C-scans. The vascular density (VD) was measured on the binarized and skeletonized angiograms of the superficial vascular plexus and deep capillary complex. The vascular diameter index (VDI) was calculated by dividing the binarized VD by the skeletonized VD. Results: On AO-FIO, cone density in the MacTel zone was significantly lower in MacTel eyes than in controls, even in areas located outside the EZ loss (P < 0.001). A distinctive pattern of IZ reflectivity attenuation extended beyond the area of EZ attenuation. The shape and size of a strong OPL hyper-reflectivity corresponded to the MacTel white area (MacTel zone) seen on BLR. Capillary dilation and rarefaction were colocalized with this area, extending beyond visible telangiectasia. The VDI was higher in MacTel eyes than in controls (P < 0.001). Conclusions: These findings suggest that in early MacTel eyes, photoreceptor signal alteration, OPL hyper-reflectivity, and capillary dilation, potentially associated with Müller cell dysfunction, precede the EZ loss.

In Vivo Visualization of Intravascular Patrolling Immune Cells in the Primate Eye.

Purpose: Insight into the immune status of the living eye is essential as we seek to understand ocular disease and develop new treatments. The nonhuman primate (NHP) is the gold standard preclinical model for therapeutic development in ophthalmology, owing to the similar visual system and immune landscape in the NHP relative to the human. Here, we demonstrate the utility of phase-contrast adaptive optics scanning light ophthalmoscope (AOSLO) to visualize immune cell dynamics on the cellular scale, label-free in the NHP. Methods: Phase-contrast AOSLO was used to image preselected areas of retinal vasculature in five NHP eyes. Images were registered to correct for eye motion, temporally averaged, and analyzed for immune cell activity. Cell counts, dimensions, velocities, and frequency per vessel were determined manually and compared between retinal arterioles and venules. Based on cell appearance and circularity index, cells were divided into three morphologies: ovoid, semicircular, and flattened. Results: Immune cells were observed migrating along vascular endothelium with and against blood flow. Cell velocity did not significantly differ between morphology or vessel type and was independent of blow flood. Venules had a significantly higher cell frequency than arterioles. A higher proportion of cells resembled "flattened" morphology in arterioles. Based on cell speeds, morphologies, and behaviors, we identified these cells as nonclassical patrolling monocytes (NCPMs). Conclusions: Phase-contrast AOSLO has the potential to reveal the once hidden behaviors of single immune cells in retinal circulation and can do so without the requirement of added contrast agents that may disrupt immune cell behavior.

MENISCUS MICROPYON: An Ophthalmoscopic Sign Possibly Associated With Epiretinal Proliferation After Retinal Surgery With Gas Tamponade.

PURPOSE: To describe an ophthalmoscopic sign, termed a meniscus micropyon, and its possible association with proliferative vitreoretinopathy/epiretinal membrane (ERM) formation after retinal surgery with gas tamponade. METHODS: Patients with intravitreal gas were examined postoperatively by one of six vitreoretinal surgeons from four institutions. A micropyon was defined as a white-yellow, solid-appearing consolidation along the meniscus (i.e., the fluid-gas interface). RESULTS: A micropyon was visualized and photographed in 49 patients who received intravitreal gas. Preoperatively, retinal breaks were present in all 49 eyes and rhegmatogenous retinal detachment in 45 (92%). Postoperatively, 39 eyes (80%) developed epiretinal proliferation: 16 eyes (33%) developed recurrent rhegmatogenous retinal detachment from proliferative vitreoretinopathy, 6 eyes (12%) re-detached without frank proliferative vitreoretinopathy, 9 eyes (18%) developed postoperative ERM/worsening, and 8 eyes (16%) had postoperative ERM but no preoperative optical coherence tomography to determine if the postoperative ERM was new or worsening. The single-operation anatomical success in eyes with a micropyon was 51%, which was lower than that of a contemporaneous rhegmatogenous retinal detachment control group (91%) in which no micropyon was detected. In two patients, micropyons were biopsied during pars plana vitrectomy and examined histopathologically; they consist predominantly of white blood cells. CONCLUSION: The meniscus micropyon is an ophthalmoscopic sign that can occur after retinal surgery with gas tamponade. Features that distinguish a micropyon from postvitrectomy fibrin/fibrinoid syndrome include delayed appearance, hyperautofluorescence, absence of translucent strands or sheets in the anterior chamber or vitreous cavity, and the histopathologic identification of white blood cells. A clinically detectable micropyon may be a biomarker of proliferative vitreoretinopathy/ERM formation.

Family of juvenile X-linked retinoschisis with varied presentation: a case series with RS1 genetic analysis.

RS1 gene mutations are known to be a direct cause of the hereditary retinopathy known as retinoschisis. We describe a group of 3 siblings with the same RS1 gene mutation who presented with different retinopathy phenotypes. Genetic testing confirmed the RS1 genotypes. Clinical ophthalmoscopy, color fundus photography, optical coherence tomography, and fundus fluorescein angiography identified manifestations of Coats-like exudative vitreoretinopathy, retinal detachment, and retinoschisis.

Multimodal High-Resolution Imaging in Retinitis Pigmentosa: A Comparison Between Optoretinography, Cone Density, and Visual Sensitivity.

Purpose: Retinitis pigmentosa (RP), the most common inherited retinal disease, is characterized by progressive photoreceptor degeneration. It remains unknown to what extent surviving photoreceptors transduce light and support vision in RP. To address this, we correlated structure and functional measures using adaptive optics scanning laser ophthalmoscopy (AOSLO), adaptive optics microperimetry, and adaptive optics optical coherence tomography (AO-OCT)-based optoretinograms (ORGs). Methods: Four patients with RP were imaged with AOSLO across the visual field covering the transition zone (TZ) of normal to diseased retina. Cone density was estimated in discrete regions spanning the TZ. Visual sensitivity was assessed by measuring increment thresholds for a 3-arcmin stimulus targeted via active eye tracking in AOSLO. ORGs were measured at the same locations using AO-OCT to assess the cones' functional response to a 528 ± 20-nm stimulus. Individual cone outer segment (COS) lengths were measured from AO-OCT in each subject. Results: Cone density was significantly reduced in patients with RP. Density reduction correlated with TZ location in 3 patients with RP, while a fourth had patches of reduced density throughout the retina. ORG amplitude was reduced in regions of normal and reduced cone density in all patients with RP. ORG response and COS length were positively correlated in controls but not in patients with RP. Despite deficits in cone density and ORG, visual sensitivity remained comparable to controls in three of four patients with RP. Conclusions: ORG-based measures of retinal dysfunction may precede deficits in cone structure and visual sensitivity. ORG is a sensitive measure of RP disease status and has significant potential to provide insight into disease progression and treatment efficacy.

Vitreoretinopathy in Asymptomatic Children With CTNNB1 Syndrome.

Importance: Previous studies have identified familial exudative vitreoretinonpathy (FEVR) in patients with CTNNB1 syndrome based on severe congenital ocular phenotypes. However, ophthalmoscopy may not be sufficient to detect vision-threatening vitreoretinopathy in all patients. Objective: To report a consecutive retrospective case series of 11 patients with CTNNB1 variants who had previously unremarkable ophthalmoscopic examination results and to describe their detailed ophthalmic phenotypes. Design, Setting, and Participants: This retrospective case series was conducted at the Children's Hospital of Philadelphia from October 2022 to November 2023 among patients with identified variants in CTNNB1 and previously documented normal results in office retinal examinations. These consecutive patients subsequently underwent an examination under anesthesia with fluorescein angiography. Detailed genotype information was analyzed for all patients, and each variant was mapped on the CTNNB1 gene to observe any associations with severity of vitreoretinopathy. Main Outcomes and Measures: Number of patients with vitreoretinopathy and number requiring treatment for vitreoretinopathy. Results: The mean (SD) age at the time of CTNNB1 syndrome diagnosis was 2 (1) years, and the mean (SD) age at examination was 6 (3) years for the 11 total patients. A total of 9 patients had a diagnosis of strabismus, and 5 patients had undergone strabismus surgery. FEVR was present in 5 of 11 patients and in 9 eyes. The presence of disease requiring treatment was identified in 6 eyes, including 1 retinal detachment. Detailed genotype analysis of the patients found no clearly delineated high-risk loci in CTNNB1 in association with high severity of FEVR. Conclusions and Relevance: In this case series study, nearly all patients with CTNNB1 syndrome required ophthalmic care for refractive error and strabismus, and a subset also required treatment for FEVR. These findings support consideration of ultra-widefield fluorescein angiography among individuals with CTNNB1 syndrome when feasible, including the use of sedation if such an assessment is not possible in the office setting.

ADAPTIVE OPTICS AND MULTIMODAL IMAGING FOR INFLAMMATORY VITREORETINAL INTERFACE ABNORMALITIES.

PURPOSE: To investigate changes to the vitreoretinal interface in uveitis with multimodal imaging including adaptive optics. METHODS: Four eyes (four patients) affected by fovea-attached (subtype 1A) or fovea-sparing epiretinal membranes (ERMs) on spectral-domain optical coherence tomography or visible internal limiting membrane (ILM) on infrared scanning laser ophthalmoscope (SLO) fundus imaging were recruited in this pilot study. The microstructure of the vitreoretinal interface was imaged using flood-illumination adaptive optics (FIAO), and the images were compared with the cross-sectional spectral-domain optical coherence tomography data. RESULTS: Adaptive optics images revealed multiple abnormalities of the vitreoretinal interface, such as deep linear striae in ERM, and hyperreflective microstructures at the location of ERMs and ILMs. The cone mosaic was imaged by FIAO and was found altered in the four eyes with ERMs or visible ILM. The same four eyes presented alteration of photopic 30 Hz flicker that was reduced in amplitude indicating cone inner retinal layer dysfunction. CONCLUSION: FIAO imaging can identify specific patterns associated with ERMs and ILMs. Correlating FIAO imaging of the vitreomacular interface with the structural alterations seen in FIAO at the level of the outer retinal structures can help understand the cause of significant macular dysfunction associated with ERM.

A method to determine the retinal radiant exposure caused by ophthalmoscopy.

PURPOSE: To introduce a method to calculate retinal irradiance caused by ophthalmoscopy. This may be used to verify the compliance of an instrument with the radiation limits set by light hazard standards. The proposed method is simpler to use and less prone to error than the methods currently found in the light hazard standards. METHODS: The optical properties of the standardised human eye, specified by current light hazard standards, are used to calculate the magnification of an aerial image of the retinal surface by the combination of the optics of eye and the auxiliary lens used for ophthalmoscopy. The magnification of the aerial image is used to transform the spectral irradiance of the instrument illumination source to retinal irradiation values. The spectral irradiance of the instrument illumination source can be measured directly as the aerial image is located in the focal plane of the viewing optics of the ophthalmoscope. These spectral irradiation values are then processed using weightings specified by current light hazard standards to give a weighted irradiance which is converted directly to a retinal irradiance value. RESULTS: A single formula is provided to calculate the retinal irradiance using the processed, measured spectral irradiance values of the illumination source. CONCLUSION: The new method introduced here is simpler to use, requires fewer physical measurements and is less likely to introduce measurement error than that currently found in light hazard standards. The only physical measurement that needs to be taken is the illumination source spectral irradiance measured in the viewing focal plane of the instrument. These values are weighted using given in the light hazard standards. The combined irradiance value is then converted to retinal irradiance using the formula given in this paper.

Are the Hypo-Reflective Clumps Associated With Age-Related Macular Degeneration in Adaptive Optics Ophthalmoscopy Autofluorescent?

Purpose: Hypo-reflective clumps (HRCs) are structures associated with age-related macular degeneration (AMD) that were identified using flood-illumination adaptive optics ophthalmoscopy (FIAO) and hypothesized to be either macrophages that have accumulated melanin through the phagocytosis of retinal pigmented epithelial (RPE) cell organelles or transdifferentiated RPE cells. HRCs may be autofluorescent (AF) in the near infrared (NIR) but clinical NIR autofluorescence imaging lacks the resolution to answer this question definitively. Here, we used near infrared autofluorescence (NIRAF) imaging in fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to determine whether HRCs are AF. Methods: Patients with AMD and HRCs underwent imaging with FIAO, optical coherence tomography (OCT), and multi-modal AOSLO (confocal, NIRAF, and non-confocal multi-offset detection using a fiber bundle). HRCs were segmented on FIAO and images, co-registered across modalities, and HRC morphometry and AF were quantified. Results: Eight patients participated (mean age = 79 years, standard deviation [SD] = 5.7, range = 69-89 years, and 5 female patients). Most HRCs (86%, n = 153/178) were autofluorescent on AOSLO. HRC AF signal varied but most uniformly dark HRCs on FIAO showed corresponding AF on AOSLO, whereas heterogeneous HRCs showed a smaller AF area or no AF. Conclusions: These findings are consistent with the hypothesis that HRCs contain AF RPE organelles. A small proportion of HRCs were not AF; these may represent macrophages that have not yet accumulated enough organelles to become AF. HRCs may have clinical significance but further study is needed to understand the interplay among HRCs, RPE cells, and macrophages, and their relationship to geographic atrophy (GA) progression in AMD.

Eyesi direct ophthalmoscope simulator: an effective training tool for medical undergraduates.

INTRODUCTION: Non-ophthalmologists often lack sufficient operational training to use a direct ophthalmoscope proficiently, resulting in a global deficit of basic ophthalmological skills among general practitioners. This deficiency hampers the timely diagnosis, referral, and intervention of patients. Consequently, the optimization of teaching tools and methods to enhance teaching efficiency is imperative. This study explores the effectiveness of the Eyesi Direct Ophthalmoscope Simulator (Eyesi) as an innovative tool for fundus examination training. METHODS: Medical undergraduates were randomly assigned to Group A or B (n = 168). All participants completed a pre-training questionnaire. Group A received Eyesi training, while Group B underwent traditional direct ophthalmoscope (TDO) training. Subsequently, participants answered questionnaires relevant to their respective training methods. Both groups exchanged training tools and completed a summary questionnaire. RESULTS: After training, 54.17% of participants believed that images presented by the Eyesi were consistent with the real fundus. Group A scored significantly higher than Group B in fundus structure recognition and self-confidence in examination. The degree of mastery over fundus theory score increased from 6.10 ± 0.13 to 7.74 ± 0.16 (P < 0.001) in Group A, but Group B did not demonstrate a significant difference. We also compared undergraduates' tendencies for different learning purposes, 75.59% of participants preferred the Eyesi to TDO as a training tool, and 88.41% of participants were receptive to introducing the Eyesi in training. CONCLUSION: According to subjective participant feedback, Eyesi outperformed TDO in fundus observation, operational practice, and theoretical learning. It effectively equips undergraduates with fundus examination skills, potentially promoting the use of direct ophthalmoscopes in primary medical institutions.

Foveolar Drusen Decrease Fixation Stability in Pre-Symptomatic AMD.

Purpose: This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD). Methods: We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO. Results: FEM were measured with high precision (RMS-S2S = 0.0015 degrees on human eyes) and small foveal drusen (median diameter = 60 µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea. Conclusions: A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

Modeling Human Macular Cone Photoreceptor Spatial Distribution.

Purpose: The purpose of this study was to investigate the spatial distribution of human cone photoreceptors and examine cone density differences between the retinal meridians and quadrants. Method: Using adaptive optics scanning laser ophthalmoscopy, the maculae were imaged in 17 eyes of 11 subjects with normal chorioretinal health aged 54 to 72 years. We measured cone density at 325 points within the central 10 degrees radius of the retina. Cone density spatial distributions along the primary retinal meridians and in four macular quadrants (superior-nasal, superior-temporal, inferior-temporal, and inferior-nasal) were analytically modeled using the polynomial function to assess the meridional and quadrantal difference. Results: The mean and 95% confidence interval for the prediction of cone density along the primary retinal meridians was modeled with a 7-degree one-variable polynomial (R2 = 0.9761, root mean squared error [RMSE] = 0.0585). In the 4 retinal quadrants, cone density distribution was described by a 2-variable polynomial with X degree 3 and Y degree 4 (R² = 0.9834, RMSE = 0.0377). The models suggest no statistically significant difference between medians and between quadrants. However, cone density difference at corresponding spatial locations in different areas can be up to 25.6%. The superior-nasal region has more areas with high cone density, followed by quadrants of inferior-nasal, inferior-temporal, and superior-temporal. Conclusions: Analytical modeling provides comprehensive knowledge of cone distribution across the entire macula. Although modeling analysis suggests no statistically significant difference between medians and between quadrants, the remarkable cone density discrepancies in certain regions should be accounted for in applications requiring sensitive detection of cone variation.

Universal eye screening: perinatal risk factors and ocular abnormalities in 1795 newborns not meeting retinopathy of prematurity criteria.

OBJECTIVES: This prospective cohort study aimed to investigate the ocular outcomes of universal eye screening in newborns and assess the relationship between different perinatal risk factors and various ocular abnormalities in infants who do not meet the criteria for retinopathy of prematurity (ROP) screening. METHODS: An universal eye screening questionnaire was utilised to screen newborn babies who did not meet the ROP screening criteria within 72 h of birth at a public and private hospital between June 2016 and April 2018. The questionnaire covered demographic characteristics, neonatal history, and eye examination findings. A trained retina specialist conducted comprehensive anterior and posterior segment examinations utilising a binocular indirect ophthalmoscope. RESULTS: Out of the 1795 newborns screened, 55.2% were male, and 44.8% were female. The most prevalent ocular abnormality observed was retinal haemorrhage (RH), with a prevalence of 10.64% (95% CI: 9.25-12.16%). The prevalence of non-RH abnormality was 7.5% (95% CI: 6.34-8.84%). The retinal haemorrhages were associated with normal vaginal deliveries (OR: 9.91; 95% CI: 6.71-14.64, p-value < 0.001), while non-RH abnormalities were associated with pre-term babies (OR: 4.87; 95% CI: 3.03-7.83, p < 0.001), consanguinity (OR: 2.20; 95% CI: 1.28-3.8, p < 0.001), low birth weight (OR: 0.22; 95% CI: 0.14-0.34, p < 0.001) and systemic abnormalities (OR: 3.08; 95% CI: 1.94-4.91, p < 0.001). CONCLUSIONS: Sight-threatening ocular pathology in newborns may be linked to perinatal risk factors such as preterm birth, low birth weight, consanguinity, and systemic abnormalities. Accordingly, it may be prudent to consider specialized ocular screening protocols for neonates within this high-risk cohort in future prospective studies.