Temporal Retina Research Articles

Midperipheral Microvascular Defects and Their Associations With Vitreoretinal Abnormalities in Early-Stage Familial Exudative Vitreoretinopathy.

To investigate microvascular growth defects in the temporal midperipheral retina and their correlations with vitreoretinal microstructural abnormalities (VRMAs) in early-stage familial exudative vitreoretinopathy (FEVR). We enrolled 127 patients (127 eyes) with early-stage FEVR and 31 healthy subjects (31 eyes). Widefield optical coherence tomography angiography was conducted for all enrolled eyes. Vessel density (VD), vessel diameter index (VDI), and vessel index (VI; VD/VDI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in temporal midperiphery were further evaluated. The distance from the vessel sprouting point of the optic disc to the avascular area margin (Optic-AVA) was measured to assess retinal vascular dysplasia. In early-stage FEVR, 61.42% of eyes showed retinal microvascular abnormalities (MVAs) in the temporal midperiphery, all combined with VRMAs. Common MVAs presented disordered vascular anastomoses in the SCP and capillary loss in the DCP, corresponding to deficient neuroretina. The preretinal vasculature (PRV) was detected in 36 eyes. VD and VI were lower in FEVR eyes compared to controls, whereas the VDI in the SCP was larger (all P < 0.001). Optic-AVA was positively correlated with VD and VI in both plexuses and negatively correlated with the VDI in the SCP. PRV existence was independently correlated with decreased VI in the DCP (odds ratio [OR] = 0.322; P < 0.001), and VRMA existence was independently correlated with decreased VI in SCP and DCP (SCP OR = 0.282, P = 0.010; DCP OR = 0.562, P = 0.002). MVAs in the temporal midperipheral retina were revealed. Microvascular loss may be correlated with Optic-AVA reduction, PRV, and the presence of VRMAs.

Retinopathy of prematurity screening: can the examination time be reduced?

ABSTRACT Clinical relevance Retinopathy of prematurity (ROP) is a significant cause of childhood blindness. Screening examinations that maintain accuracy, while improving the experience for families, could increase adherence to follow-up and decrease workload. Background Traditional ROP screening examinations are known to be uncomfortable for babies and stressful for parents. A new strategy is proposed and tested for the accuracy of the outcome and the time taken. Methods In this new screening strategy, the examiner performs a complete retinal examination on the first visit. If the area and stage of the nasal and temporal retinal regions are similar or the stage of the temporal half is worse, only the posterior pole and temporal half of the retina are evaluated at subsequent visits. A retrospective patient file review was conducted to compare the new proposal with accepted methods. ROP examination time was compared prospectively. Results The data of 57 consecutive patients treated for ROP were evaluated. The ROP zone was the same in the nasal and temporal retina in all eyes at the first and last visit before treatment. Only two eyes had worse ROP stage in the nasal half at presentation but both halves developed the same degree of stage during follow-up. None of the treatment decisions were based only on the nasal region of the retina. Examination time was evaluated in 40 eyes of 20 infants. The average total time required for an examination with the accepted method was 241.3 ± 112.5 seconds. However, with the proposed strategy, the examination time was significantly reduced to 172.3 ± 69.2 seconds (p < 0.001). Conclusions This screening strategy shortens examination time, which may help reduce pain and related adverse events.

Optical coherence tomography (OCT) and OCT Angiography in Stages 3 and 4 proliferative sickle cell retinopathy

PurposeTo investigate macular findings in Goldberg stages 3 and 4 proliferative sickle cell retinopathy (PSCR) using optical coherence tomography (OCT) and OCT Angiography MethodsA case-control study using retrospective OCT and OCTA data from PSCR eyes (cases) and prospective data from age and sex-matched normal (controls). OCTA data included vessel density (VD) in the superficial capillary vascular plexus (SCP) and deep capillary vascular plexus (DCP), foveal avascular zone (FAZ) characterization, including the shape (in the SCP & DCP), size (area covered), and perimeter. OCT data were whole, superior, and inferior hemi-retina thickness for the superficial and deep retina. ResultsThere were 38 OCT / OCTA scans of PSCR eyes of 21 SCD patients; ten eyes were excluded for not meeting inclusion criteria. We analyzed nineteen (19) patients (ten unilateral and 9 bilateral), 28 eyes, nine SS eyes (32%), and nineteen SC eyes (68%). The controls consisted of 29 eyes of 16 normal subjects (three unilateral and 13 bilateral). The commonest FAZ shape in PSCR was “irregular” in 14 eyes (50%), followed by “round” in 11 eyes (39.3%) versus controls, the commonest shape “round” in 18 eyes (62%), followed by “irregular” 9 eyes (31%) (p = 0.165). FAZ area and perimeter were larger in PSCR (p > 0.05). The deep and superficial VD was reduced in PSCR. The mean whole deep VD for cases was 48.9 ± 6.1 versus 52.9 ± 6.4 for controls (p = 0.019). Mean whole superficial VD for cases was 47.4 ± 5.5 versus 49.8 ± 3.4 for controls (p = 0.058).Retina thickness in the whole, superior and inferior hemi-retina, for superficial and deep retina, was higher in PSCR compared to controls (p < 0.05). Superficial whole thickness for cases and controls were 287.0 µm [IQR 35.3 µm] versus 273.0 µm [IQR 18 µm] respectively (p = 0.008). Deep whole thickness for cases and controls was 287.0 µm [IQR 35.25 µm] versus 273.0 µm [IQR 18 µm] (p = 0.008).VD was reduced in SS compared to SC eyes (deep whole VD: 50.28 ± 6.01 vs 46.78 ± 5.80) (p = 0.139). Retina thickness in SS was reduced relative to SC. Peripheral retinal laser photocoagulation did not affect VD, though it was associated with a thinner macula. ConclusionOCT/OCTA of stage 3 and 4 PSCR revealed reduced VD in the DCP and SCP. Despite the thin temporal retina in SCD, there is a thicker whole, superior, and inferior hemiretina in both the superficial and deep retina. An irregularly shaped FAZ is common, a reflection of abnormal microcapillary loss in the perifoveal area.

Frequency-dependent effects of 0.05% atropine eyedrops on myopia progression and peripheral defocus: a prospective study

BackgroundAtropine, specifically 0.05% eyedrops, has proven effective in slowing myopia progression. This study aims to investigate peripheral refraction (PR) characteristics in myopic children treated with 0.05% atropine eyedrops at different frequencies.MethodsOne hundred thirty-eight myopic children completed this one-year prospective study, randomly assigned to once daily (7/7), twice per week (2/7), or once per week (1/7) groups. Spherical equivalent (SE) and axial length (AL) were measured. PR was assessed using a custom-made Hartmann-Shack wavefront peripheral sensor, covering a visual field of horizontal 60° and vertical 36°. Relative peripheral refraction (RPR) was calculated by subtracting central from peripheral measurements.ResultsAfter one year, SE increased more significantly in the 1/7 group compared to the 7/7 group (P < 0.001) and 2/7 group (P = 0.004); AL elongation was also greater in the 1/7 group compared to the 7/7 group (P < 0.001). In comparison with higher frequency groups, 1/7 group exhibited more myopic PR in the fovea and its vertical superior, inferior, and nasal retina; and less myopic RPR in the periphery retina after one-year (P < 0.05). Additionally, RPR in the 7/7 group demonstrated myopic shift across the entire retina, the 2/7 group in temporal and inferior retina, while the 1/7 group showed a hyperopic shift in the superior retina (P < 0.05). Moreover, myopic shift of RPR in the temporal retina is related to less myopia progression, notably in the 7/7 group (P < 0.05).ConclusionsAtropine inhibits myopia progression in a frequency-dependent manner. The once-daily group showed the slowest myopia progression but exhibited more myopic shifts in RPR. Additionally, RPR in the temporal retina was related to myopia progression in all groups.Trial registrationChinese Clinical Trial Registry, ChiCTR2100043506. Registered 21 February 2021, https://www.chictr.org.cn/showproj.html?proj=122214

Analysis of the peripheral refraction in myopic adults using a novel multispectral refraction topography

PurposeTo determine the distribution and characteristics of peripheral refraction in adults with myopia using the novel multispectral refraction topography. MethodA total of 187 adults with myopia were recruited for this study. This study was conducted in two stages. Part I: participants were divided into 6 groups based on the central refraction of the right eyes, Part II: according to the interocular differences in refractive error (IOD) of the central refraction, we divided the participants into isomyopia group (IOD<1.00 D) and anisomyopia group (IOD≥1.0 D). We surveyed the characteristics of peripheral refraction and relative peripheral refraction (RPR), as well as the correlation between RPR and central refraction, age, sex, and axial length. ResultPart I: With an increase in the degree of myopia, relative peripheral hyperopia developed from the center to the periphery. A statistically significant hyperopia shift compared to the center (P < 0.05) was first observed on the temporal side within a 40° field of view at the posterior pole of the retina. The RPR of the temporal, superior, and inferior retinas positively correlated only with age. Part II: In the isomyopic participants, there was no difference in peripheral refraction between the eyes (P < 0.05). In the anisomyopic participants, the RPR of the more myopic eyes was more hyperopic than that of the less myopic eyes in NRDV40-50, SRDV10-20, SRDV30-50, TRDV20-30, TRDV40-50, and IRDV10-40. ConclusionWith an increase in the degree of myopia, relative peripheral hyperopia developed from the center to the periphery, and peripheral refraction progressed at different rates in various retinal zones.

Angiographic Characteristics in Mild Familial Exudative Vitreoretinopathy with Genetically Confirmed Autosomal Dominant Inheritance

PurposeTo determine the ultra-widefield fluorescein angiographic (UWFA) characteristics of patients with mild familial exudative vitreoretinopathy (FEVR) who had been confirmed to have pathogenic variants of the autosomal dominant (AD) genes of FEVR. DesignSingle center, observational case series. Subjects and ControlsThirty-seven patients with mild FEVR from 27 families who had pathogenic variants of the Norrin/β-catenin genes were studied. The controls consisted of 32 family members who had been confirmed not to carry the pathogenic variants or had heterozygous variants of the autosomal recessive inheritance gene. MethodsSixty-four UWFA images from the patients were compared to 60 UWFA images from the controls. The relative length of the temporal retina to the peripheral avascular retina was determined. The cut-off ratio of the relative lengths for a clinically significant avascular retina (csAR) associated with AD-FEVR was determined using the receiver operating characteristic (ROC) curves. Main Outcome MeasuresThe presence or absence of six peripheral vascular changes: csAR, V-shaped vascular notch, brushy vascular ends, vascular stain, loop vessels and/or anastomosis, and capillary telangiectasia were compared between the patients and the controls. ResultsThe csAR was set at >12% of the length from the ora serrata to the optic disc. The AD-FEVR patients had more frequent retinal changes than the controls for the V-shaped vascular notch (69% vs 2%, P <0.001), brushy vascular ends (78% vs 3%, P <0.001), csAR (83% vs 22%, P <0.001), and vascular stain (70% vs 33%, P <0.001). Loop vessels and/or anastomosis of peripheral vessels were found significantly less frequently in the patients than in the controls (39% vs 73%, P <0.001). No significant difference was found for capillary telangiectasia between the two groups. The combination of the V-shaped vascular notches, brushy vascular ends, and csAR had a sensitivity of 82.8% and specificity of 98.3% with the highest ROC curve of 0.9. ConclusionsThe combination of V-shaped vascular notch, brushy vascular ends, and csAR can be used as a biomarker for AD-FEVR patients who have pathogenic variants of the Norrin/β-catenin genes. These findings will allow more accurate segregation analysis in FEVR families and allow better genetic counseling.

Non-syndromic OTX2-associated pattern dystrophy: a 10-year multimodal imaging study

PurposeTo report novel multimodal imaging features and long-term follow-up of Orthodenticle Homeobox 2 (OTX2)-associated pattern Gdystrophy.MethodsA 14-year-old boy referred with glaucoma suspect and macular pigmentation underwent fundus autofluorescence imaging, optical coherence tomography, fluorescein and indocyanine green angiography, visual field test, microperimetry and electrophysiology over a ten-year period. Next-generation sequencing panel identified a de novo heterozygous likely pathogenic OTX2 variant, c.259G>A, [p.(Glu87Lys)].ResultsVisual acuity was 20/40 OD and 20/30 OS. Examination showed bilateral enlarged optic nerve heads and increased disc cupping, multiple cilioretinal arteries, a pigmentary maculopathy with stellate-shaped region of hypoautofluorescence, shallow serous macular detachment, subretinal deposits and temporal avascular retina. Angiography showed no source of leakage and absence of retinal neovascularisation despite extensive peripheral non perfusion. Electrophysiological assessments demonstrated mild progressive rod and cone pathway abnormalities, reduced light-adapted b:a ratio, and reduced Arden ratio on electro-oculogram. Ten-year follow-up confirmed a stable disease course despite persistent submacular fluid. There was no associated pituitary structural abnormality or dysfunction.ConclusionsThis case study contributes to further understanding of OTX2-associated pattern dystrophy, highlighting its stability over 10 years. Further investigation into inter-individual and intrafamilial variability is warranted.

Investigating the impact of asymmetric macular sensitivity on visual acuity chart reading in choroideremia.

Degeneration in choroideremia, unlike typical centripetal photoreceptor degenerations, is centred temporal to the fovea. Once the fovea is affected, the nasal visual field (temporal retina) is relatively spared, and the preferred retinal locus shifts temporally. Therefore, when reading left to right, only the right eye reads into a scotoma. We investigate how this unique property affects the ability to read an eye chart. Standard- and low-luminance visual acuity (VA) for right and left eyes were measured with the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Letters in each line were labelled by column position. The numbers of letter errors for each position across the whole chart were summed to produce total column error scores for each participant. Macular sensitivity was assessed using microperimetry. Central sensitivity asymmetry was determined by the temporal-versus-nasal central macular difference and subsequently correlated to a weighted ETDRS column error score. Healthy volunteers and participants with X-linked retinitis pigmentosa GTPase regulator associated retinitis pigmentosa (RPGR-RP) were used as controls. Thirty-nine choroideremia participants (median age 44.9 years [IQR 35.7-53.5]), 23 RPGR-RP participants (median age 30.8 years [IQR 26.5-40.5]) and 35 healthy controls (median age 23.8 years [IQR 20.3-29.0]) were examined. In choroideremia, standard VA in the right eye showed significantly greater ETDRS column errors on the temporal side compared with the nasal side (p = 0.002). This significantly correlated with greater asymmetry in temporal-versus-nasal central macular sensitivity (p = 0.04). No significant patterns in ETDRS column errors or central macular sensitivity were seen in the choroideremia left eyes, nor in RPGR-RP and control eyes. Difficulty in tracking across lines during ETDRS VA testing may cause excess errors independent of true VA. VA assessment with single-letter optotype systems may be more suitable, particularly for patients with choroideremia, and potentially other retinal diseases with asymmetric central macular sensitivity or large central scotomas including geographic atrophy.

Linking Vascular Structure and Function: Image-Based Virtual Populations of the Retina.

This study explored the relationship among microvascular parameters as delineated by optical coherence tomography angiography (OCTA) and retinal perfusion. Here, we introduce a versatile framework to examine the interplay between the retinal vascular structure and function by generating virtual vasculatures from central retinal vessels to macular capillaries. Also, we have developed a hemodynamics model that evaluates the associations between vascular morphology and retinal perfusion. The generation of the vasculature is based on the distribution of four clinical parameters pertaining to the dimension and blood pressure of the central retinal vessels, constructive constrained optimization, and Voronoi diagrams. Arterial and venous trees are generated in the temporal retina and connected through three layers of capillaries at different depths in the macula. The correlations between total retinal blood flow and macular flow fraction and vascular morphology are derived as Spearman rank coefficients, and uncertainty from input parameters is quantified. A virtual cohort of 200 healthy vasculatures was generated. Means and standard deviations for retinal blood flow and macular flow fraction were 20.80 ± 7.86 µL/min and 15.04% ± 5.42%, respectively. Retinal blood flow was correlated with vessel area density, vessel diameter index, fractal dimension, and vessel caliber index. The macular flow fraction was not correlated with any morphological metrics. The proposed framework is able to reproduce vascular networks in the macula that are morphologically and functionally similar to real vasculature. The framework provides quantitative insights into how macular perfusion can be affected by changes in vascular morphology delineated on OCTA.

Autophagy and Exocytosis of Lipofuscin Into the Basolateral Extracellular Space of Human Retinal Pigment Epithelium From Fetal Development to Adolescence.

To undertake the first ultrastructural characterization of human retinal pigment epithelial (RPE) differentiation from fetal development to adolescence. Ten fetal eyes and three eyes aged six, nine, and 17 years were examined in the temporal retina adjacent to the optic nerve head by transmission electron microscopy. The area, number, and distribution of RPE organelles were quantified and interpreted within the context of adjacent photoreceptors, Bruch's membrane, and choriocapillaris maturation. Between eight to 12 weeks' gestation (WG), pseudostratified columnar epithelia with apical tight junctions differentiate to a simple cuboidal epithelium with random distribution of melanosomes and mitochondria. Between 12 to 26 WG, cells enlarge and show long apical microvilli and apicolateral junctional complexes. Coinciding with eye opening at 26 WG, melanosomes migrate apically whereas mitochondria distribute to perinuclear regions, with the first appearance of phagosomes, complex granules, and basolateral extracellular space (BES) formation. Significantly, autophagy and heterophagy, as evidenced by organelle recycling, and the gold standard of ultrastructural evidence for autophagy of double-membrane autophagosomes and mitophagosomes were evident from 32 WG, followed by basal infoldings of RPE cell membrane at 36 WG. Lipofuscin formation and deposition into the BES evident at six years increased at 17 years. We provide compelling ultrastructural evidence that heterophagy and autophagy begins in the third trimester of human fetal development and that deposition of cellular byproducts into the extracellular space of RPE takes place via exocytosis. Transplanted RPE cells must also demonstrate the capacity to subserve autophagic and heterophagic functions for effective disease mitigation.

Mechanical Ventilation, Retinal Avascularity and Rate of Vascularisation: A Triad of Predictors for Retinopathy of Prematurity Treatment.

The temporal avascular area of the retina and the duration of mechanical ventilation (DMV) may predict the need to treat retinopathy of prematurity (ROP). This study considers whether the rate of retinal vascularisation and related risk factors should be included in a predictive model of the need for ROP treatment. This single-centre, observational retrospective case-control study was conducted on 276 preterm infants included in an ROP screening programme. All had undergone at least three examinations of the fundus. The main outcome measures considered were DMV (in days of treatment), the temporal avascular area (in disc diameters, DD) and the rate of temporal retinal vascularisation (DD/week). The multivariate logistic model that best explains ROP treatment (R2 = 63.1%) has three significant risk factors: each additional day of mechanical ventilation (OR, 1.05 [95% CI, 1.02-1.09]; p = 0.001); each additional DD of temporal avascular area (OR, 2.2 [95% CI, 1.7-2.9]; p < 0.001) and a vascularisation rate <0.5 DD/week (OR, 19.0 [95% CI, 6.5-55.5]; p < 0.001). Two tables are presented for calculating the expected need for ROP treatment according to these three risk factors. A greater DMV, a broad avascular area of the temporal retina at the first binocular screening and slow retinal vascularisation strongly predict the need for ROP treatment. The predictive model we describe must be validated externally in other centres.

Quantitative Analysis of the Vasculature and Cone Photoreceptors in Subjects With Diabetes Without Diabetic Retinopathy

Purpose To characterize any differences in the vasculature and cone photoreceptor packing geometry (CPG) between subjects with diabetes without/no diabetic retinopathy (NDR) and healthy controls. Methods Eight NDR and five controls were enrolled. Optical coherence tomography angiography (OCTA) taken at the macula was used to measure vessel density, vessel length density, and vessel density index (VDI) in three vascular plexuses, namely, the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus (DCP). The choriocapillaris (CC) flow deficit (FD) was also measured. OCTA images were binarized and processed to extrapolate the parafovea and parafoveal quadrants and the OCTA indices mentioned above. The CC was processed with six different radii to quantify FD. Adaptive optics - scanning laser ophthalmoscopy images were acquired and processed to extract CPG indices, i.e., cone density (CD), cone-to-cone spacing (CS), linear dispersion index, heterogeneity packing index and percent of cells with six neighbors at 3.6° in the temporal retina. Results In all eyes, statistically significant differences were found (i) in parafoveal FD across the six radii (p < 0.001) and (ii) in the correlation between the parafoveal temporal quadrant (PTQ) DCP VDI and CS (r = 0.606, p = 0.048). No other significant correlations were found. For OCTA or CPG indices, no significant differences were found between the cohorts in the parafovea or parafoveal quadrants. Conclusions CS is the most sensitive CPG index for detecting alterations in the cone mosaic. The DCP and the cone photoreceptors are significantly correlated, indicating that alterations in the DCP can affect the cones. Future work elucidating the vascular alterations and neurodegeneration present in diabetic eyes should focus on the DCP and multiple CPG indices, not solely CD. Moreover, such alterations are highly localized, hence using larger regions e.g. parafovea versus smaller areas, such as the PTQ, will potentially mask significant correlations.

Type 1 and type 2 torpedo maculopathy.

To analyze torpedo maculopathy (TM) and to report the characteristics of the disease. Retrospective study. The review of a database for clinical diagnosis identified eight patients with TM lesions in the retina between 2016 and 2022. Multimodal imaging was used to analyze the cases. All cases were unilateral, asymptomatic, and hypopigmented. They were associated by surrounding hyperpigmented retinal pigment epithelium changes to varying degrees. All lesions were located in the temporal retina on the horizontal axis, pointing towards the fovea, except for one patient with a lesion inferior to the fovea. Optical coherence tomography imaging revealed a normal inner retina in all eyes. In the area of the TM lesion, attenuation of the interdigitation zone was seen in mild cases (three cases). All other five patients had thinning of the outer nuclear layer and loss of ellipsoid zone and interdigitation zone of the TM lesion. Four of these cases had a subretinal cavitation/cleft, and two of them additionally an inner choroidal excavation. No patient had any sign of choroidal neovascularization. The average age for patients with type 1 TM was 18years and for type 2 TM 16.5years. In this large case series, we could not detect an age difference between the different types of the TM. Contrary to previous discussions, type 2 TM can also occur in young patients.

Aniseikonia and retinal morphological changes in eyes undergoing macular hole surgery

Even after idiopathic macular hole (MH) surgery and with successful closure of MH, aniseikonia is a common postoperative symptom. We investigated the correlation of MH diameter, retinal displacement and retinal layer thicknesses with aniseikonia in 41 eyes of 41 patients undergoing MH surgery with internal limiting membrane peeling. Aniseikonia was measured with the New Aniseikonia Test. Retinal displacement (RD%) was defined as change of retinal distance between the temporal margin of the optic papilla and the intersection of the retinal vessels. Changes of thicknesses of the inner nuclear layer (INL%) and the outer retinal layer (OR%) were calculated. Aniseikonia improved postoperatively. Preoperative aniseikonia and their improvement at 6 months correlated with MH diameters (P = 0.004–0.046). Improvement of aniseikonia correlated with temporal RD% (P = 0.002–0.012). Improvement of vertical aniseikonia correlated with INL% at 2 weeks and with the nasal OR% at 1, 3, and 6 months (P = < 0.001–0.028). MH diameter and age were significant predictors for improvement of aniseikonia. The greater the temporal retina displacement, and the thinner the postoperative INL and OR, the greater the improvement of aniseikonia. MH diameter and age are strong predictors for improvement of aniseikonia after MH surgery.

Study of peripheral blur in retinal electrical activity

Aims/Purpose: The aim of this study was to evaluate changes in peripheral refraction by the use of a contact lens to control the progression of myopia. In addition, the response of electrophysiological activity in different areas of the retina with and without contact lens was also determined.Methods: We recruited 7 myopic individuals (23.71 ± 5.41 years) with refraction up to −4.50D (spherical equivalent), without eye pathologies and surgeries. Visual acuity was recorded, high and low contrast, with the updated refraction and with the Misight 1 Day contact lens. Peripheral refraction measurements were obtained using an open‐field autorefractometer. Multifocal electrophysiology measurements were performed binocularly with and without contact lens, with dilated pupil. Topography and aberrometry values were also recorded.Results: lens, peripheral refractions become significantly more myopic. The change in peripheral refraction induced at 30° Nasal is −0.66D. High Contrast Visual Acuity was always superior to Low Contrast VA in both conditions. The Misight 1 Day contact lens manifests a different behaviour along the anterior surface of the cornea. LC induces a significant increase in high‐order aberrations, especially in comatic aberrations, which increase three times their initial value.Conclusions: Regarding the electrophysiological response of the retina, with the use of the LC Misight 1 Day, it presented a greater implicit time and amplitude of the P1 component, in the superior temporal retina, these differences being statistically significant. The implicit time of the P2 component increased in the temporal retina and in the retinal area delimited by Rings 3, 4 and 5.

Treatment Strategy With Gene Editing for Late-Onset Retinal Degeneration Caused by a Founder Variant in C1QTNF5.

Genome editing is an emerging group of technologies with the potential to ameliorate dominant, monogenic human diseases such as late-onset retinal degeneration (L-ORD). The goal of this study was to identify disease stages and retinal locations optimal for evaluating the efficacy of a future genome editing trial. Twenty five L-ORD patients (age range, 33-77 years; median age, 59 years) harboring the founder variant S163R in C1QTNF5 were enrolled from three centers in the United Kingdom and United States. Patients were examined with widefield optical coherence tomography (OCT) and chromatic perimetry under dark-adapted and light-adapted conditions to derive phenomaps of retinal disease. Results were analyzed with a model of a shared natural history of a single delayed exponential across all subjects and all retinal locations. Critical age for the initiation of photoreceptor loss ranged from 48years at the temporal paramacular retina to 74 years at the inferior midperipheral retina. Subretinal deposits (sRET-Ds) became more prevalent as critical age was approached. Subretinal pigment epithelial deposits (sRPE-Ds) were detectable in the youngest patients showing no other structural or functional abnormalities at the retina. The sRPE-D thickness continuously increased, reaching 25µm in the extrafoveal retina and 19µm in the fovea at critical age. Loss of light sensitivity preceded shortening of outer segments and loss of photoreceptors by more than a decade. Retinal regions providing an ideal treatment window exist across all severity stages of L-ORD.

Longitudinal Changes of Retinal Structure in Molecularly Confirmed C1QTNF5 Patients With Late-Onset Retinal Degeneration.

The purpose of this study was to present our findings on the natural history of late-onset retinal degeneration (LORD) in patients with molecularly confirmed C1QTNF5 heterozygous pathogenic variants and assess suitability of retinal structure parameters for disease monitoring. Sixteen patients with C1QTNF5-LORD were retrospectively identified from Moorfields Eye Hospital, UK. Fundus autofluorescence (FAF), optical coherence tomography (OCT) scans, and best-corrected visual acuity (BCVA) were collected. Area of atrophy (AA) was manually drawn in FAF images. Ellipsoid zone (EZ) width and foveal retinal thickness of the whole retina and outer retina were extracted from OCT scans. Age-related changes were tested with linear-mixed models. Patients had median age of 62.3years (interquartile range [IQR]=58.8-65.4years) at baseline, and median follow-up of 5.1years (IQR=2.6-7.6years). AA, EZ width, and retinal thickness parameters remained unchanged until age 50years, but showed significant change with age thereafter (all P < 0.0001). AA and EZ width progressed rapidly (dynamic range normalized rates=4.3-4.5%/year) from age 53.9 and 50.8years (estimated inflection points), respectively. Retinal thickness parameters showed slower progression rates (range=1.6-2.5%/year) from age 60 to 62.3. BCVA (median=0.3 LogMAR, IQR=0.0-1.0 at baseline) showed a rapid decline (3.3%) from age 70years. Findings from patients with earlier disease showed FAF atrophy manifests in the temporal retina initially, and then progresses nasally. Patients with LORD remained asymptomatic until age 50years, before suffering rapid outer retinal degeneration. EZ width and AA showed rapid progression and high interocular correlation, representing promising outcome metrics. Clinical measures also capturing the temporal retina may be preferable, enabling earlier detection and better disease monitoring. Area of atrophy in FAF images and OCT-measured EZ width represent promising outcome metrics for disease monitoring in patients with C1QTNF5-LORD.

Development and validation of an artificial intelligence based screening tool for detection of retinopathy of prematurity in a South Indian population.

The primary objective of this study was to develop and validate an AI algorithm as a screening tool for the detection of retinopathy of prematurity (ROP). Images were collected from infants enrolled in the KIDROP tele-ROP screening program. We developed a deep learning (DL) algorithm with 227,326 wide-field images from multiple camera systems obtained from the KIDROP tele-ROP screening program in India over an 11-year period. 37,477 temporal retina images were utilized with the dataset split into train (n = 25,982, 69.33%), validation (n = 4,006, 10.69%), and an independent test set (n = 7,489, 19.98%). The algorithm consists of a binary classifier that distinguishes between the presence of ROP (Stages 1-3) and the absence of ROP. The image labels were retrieved from the daily registers of the tele-ROP program. They consist of per-eye diagnoses provided by trained ROP graders based on all images captured during the screening session. Infants requiring treatment and a proportion of those not requiring urgent referral had an additional confirmatory diagnosis from an ROP specialist. Of the 7,489 temporal images analyzed in the test set, 2,249 (30.0%) images showed the presence of ROP. The sensitivity and specificity to detect ROP was 91.46% (95% CI: 90.23%-92.59%) and 91.22% (95% CI: 90.42%-91.97%), respectively, while the positive predictive value (PPV) was 81.72% (95% CI: 80.37%-83.00%), negative predictive value (NPV) was 96.14% (95% CI: 95.60%-96.61%) and the AUROC was 0.970. The novel ROP screening algorithm demonstrated high sensitivity and specificity in detecting the presence of ROP. A prospective clinical validation in a real-world tele-ROP platform is under consideration. It has the potential to lower the number of screening sessions required to be conducted by a specialist for a high-risk preterm infant thus significantly improving workflow efficiency.

One-year results for myopia control with aspheric base curve orthokeratology lenses: A prospective randomised clinical trial.

To compare the effect of orthokeratology (ortho-k) using aspheric or spherical base curve (BCA vs. BCS) contact lenses on axial elongation and the relative peripheral refraction change (RPRC) in Chinese children. Children aged 8-12 years with myopia between -0.75 and -4.00 D and astigmatism ≤1.00 D were randomly assigned to the BCA or BCS group. Peripheral refraction was assessed at 10°, 20° and 30° along the temporal and nasal retina at baseline and at the 12-month visit. Axial length (AL) was measured under cycloplegia at baseline and at the 6- and 12-month visits. Only right eye data were analysed. Repeated-measures analysis of covariance was performed to examine the differences in axial elongation and the RPRC between the BCA and BCS groups. The 1-year results from 31 BCA and 32 BCS subjects were analysed. No significant between-group differences were found at baseline (p ≥ 0.28). At the 12-month visit, the BCA lens produced a greater absolute RPRC along the horizontal meridian than the BCS lens (p < 0.001). Axial elongation was slower in the BCA group (0.19 ± 0.20 mm) than in the BCS group (0.29 ± 0.14 mm; p = 0.03). Axial elongation was correlated with the RPRC at 10° (r = 0.43, p = 0.02) and 20° (r = 0.39, p = 0.03) along the temporal retina in the BCA group; however, these correlations were not observed in the BCS group. The BCA ortho-k lens could improve the efficacy of slowing axial elongation in children. The improved myopia control observed in the BCA group may be the result of a larger myopic shift in relative peripheral refraction within 20° along the temporal retina.

Coats-like Vasculopathy in Inherited Retinal Disease: Prevalence, Characteristics, Genetics, and Management

To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV). Multicenter retrospective cohort study. A total of 67 patients with IRD-related CLV. Review of clinical notes, ophthalmic imaging, and molecular diagnosis from 2 international centers. Visual function, retinal imaging, management, and response to treatment were evaluated and correlated. The prevalence of IRD-related CLV was 0.5%; 54% of patients had isolated retinitis pigmentosa (RP), 21% had early-onset severe retinal dystrophy, and less frequent presentations were syndromic RP, sector RP, cone-rod dystrophy, achromatopsia, PAX6-related dystrophy, and X-linked retinoschisis. The overall age of patients at CLV diagnosis was 30.7 ± 16.9 years (1-83). Twenty-one patients (31%) had unilateral CLV, and the most common retinal features were telangiectasia, exudates, and exudative retinal detachment (ERD) affecting the inferior and temporal retina. Macular edema/schisis was observed in 26% of the eyes, and ERD was observed in 63% of the eyes. Fifty-four patients (81%) had genetic testing, 40 of whom were molecularly solved. Sixty-six eyes (58%) were observed, 17 eyes (15%) were treated with a single modality, and 30 eyes (27%) had a combined approach. Thirty-five eyes (31%) were "good responders," 42 eyes (37%) were "poor responders," 22 eyes (19%) had low vision at baseline and were only observed, and 12 eyes (11%) did not have longitudinal assessment. Twenty-one observed eyes (62%) responded well versus 14 (33%) treated eyes. Final best-corrected visual acuity was significantly worse than baseline (P = 0.002); 40 patients (60%) lost 15 ETDRS letters or more over follow-up in 1 or both eyes, and 21 patients (31%) progressed to more advanced stages of visual impairment. Inherited retinal disease-related CLV is rare, sporadic, and mostly bilateral; there is no gender predominance, and it can occur in diverse types of IRD at any point of the disease, with a mean onset in the fourth decade of life. Patients with IRD-related CLV who have decreased initial visual acuity, ERD, CLV changes affecting 2 or more retinal quadrants, and CRB1-retinopathy may be at higher risk of a poor prognosis. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.