Efficacy of anti-suppression therapy in improving binocular vision in children with small-angle Esotropia

Purpose: To evaluate the efficacy of anti-suppression exercises in children with small-angle esotropia in achieving binocular vision. Methods: A retrospective review of patients aged 3–8 years who underwent anti-suppression exercises for either monocular or alternate suppression between January 2016 and December 2021 was conducted. Patients with esotropia less than 15 prism diopters (PD) and visual acuity ≥ 6/12 were included. Patients with previous intra-ocular surgery or less than three-month follow-up were excluded. Success was defined as the development of binocular single vision (BSV) for distance, near, or both (measured clinically with either the 4 prism base out test or Worth four dot test) and maintained at two consecutive visits. Qualified success was defined as the presence of diplopia response for both distance and near. Additionally, improvement in near stereo acuity was measured using the Stereo Fly test. Results: Eighteen patients with a mean age of 5.4 ± 1.38 years (range 3–8 years) at the time of initiation of exercises were included in the study. The male female ratio was 10:8. The mean best corrected visual acuity was 0.18 LogMAR unit(s) and the mean spherical equivalent was +3.8 ± 0.14 diopters (D). The etiology of the esotropia was fully accommodative refractive esotropia (8), microtropia (1), post–operative infantile esotropia (4), partially accommodative esotropia (1), and post-operative partially accommodative esotropia (4). Patients received either office-based, home-based, or both modes of treatment for an average duration of 4.8 months (range 3–8). After therapy, BSV was achieved for either distance or near in 66.6 % of patients (95 % CI = 40.03–93.31 %). Binocular single vision for both distance and near was seen in 50 % of children. Qualified success was observed in 38.46% of patients. Persistence of suppression was observed in one patient (5.5 %)... (AU)

MDSCs promote pathological angiogenesis in ocular neovascular disease.

BACKGROUND: Ocular neovascular diseases, which contribute significantly to vision loss, lack effective preventive treatments. Recent studies have highlighted the significant involvement of immune cells in neovascular retinopathy. Myeloid-derived suppressor cells (MDSCs) promote the development of neovascularization, but it is unknown whether they participate in pathological neovascularization and whether they are expected to be a therapeutic target. METHOD: We investigated the role of MDSCs in promoting pathological angiogenesis using an oxygen-induced retinopathy (OIR) model, employing flow cytometry, immunofluorescence, and smart-seq analysis. Then, we evaluated the proportion of MDSCs in patient blood samples using flow cytometry. Additionally, we assessed the effect of MDSC depletion using an anti-Gr-1 monoclonal antibody on retinal vasculopathy and alterations in retinal microglia. RESULTS: In the OIR model, an elevated ratio of MDSCs was observed in both blood and retinal tissue during phase II (Neovascularization). The depletion of MDSCs resulted in reduced retinal neovascularization and vaso-obliteration, along with a decrease in microglia within the neovascularization area. Furthermore, analysis of gene transcripts associated with MDSCs indicated activation of vascular endothelial growth factor (VEGF) regulation and inflammation. Importantly, infants with ROP exhibited a higher proportion of MDSCs in their blood samples. CONCLUSION: Our results suggested that excessive MDSCs represent an unrecognized feature of ocular neovascular diseases and be responsible for the retinal vascular inflammation and angiogenesis, providing opportunities for new therapeutic approaches to ocular neovascular disease.

Using multi-modal imaging to refine the phenotype of PRPH2-associated retinal degeneration.

OBJECTIVE: To refine retinal PRPH2-associated retinal degeneration (PARD) phenotypes using multimodal imaging. DESIGN: Retrospective review of clinical records and multimodal imaging. SUBJECTS: Patients who visited the inherited retinal degeneration (IRD) clinic at two tertiary referral eye centers with molecularly confirmed IRD due to PRPH2 variants. METHODS: Retinal imaging was reviewed using ultra-widefield (UWF) pseudocolor, UWF fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Phenotypes were identified in the macular or peripheral region. A combined phenotype was considered if any phenotypes were present in both macular and peripheral regions. Mixed phenotypes in the macula or peripheral retina were considered if there were two distinct phenotypes identified in the same eye. The presence or absence of atrophy in the macular or peripheral area was also noted. MAIN OUTCOME MEASURE: Grading of multimodal imaging by phenotype and atrophy. RESULTS: A total of 144 eyes of 72 patients were included in this study. The majority of the eyes had combined macular and peripheral phenotypes (89/14, 61.8%), while 44 (30.6%) eyes had isolated macular findings, and 11 (7.6%) had isolated peripheral findings. Twenty-five eyes were classified with mixed macular phenotypes while fundus flavimaculatus dystrophy type was the most common combined macular and peripheral phenotype (54/144, 37.5%): n = 10 with macular dystrophy and macular flavimaculatus dystrophy, and n = 15 with butterfly pattern dystrophy and macular flavimaculatus dystrophy. Nearly half of the eyes (71/144, 49.3%) were identified to have concomitant outer retinal atrophy. Fundus flavimaculatus type dystrophy was also associated with the highest proportion of concomitant atrophy (57/71, 80.3%). CONCLUSION: PARD demonstrates a wide array of phenotypes using multimodal imaging. We report that combinations of classically described phenotypes were often seen. Additionally, macular and peripheral atrophy were often associated with PARD phenotypes. Refinement of PARD phenotypes using newer multimodal imaging techniques will likely assist diagnosis and future clinical trials.

Systematic Literature Reviews Comparing the Long-Term Safety Outcomes for the Port Delivery System with Ranibizumab (PDS) Versus Other Ocular Implants.

OBJECTIVES: To determine whether the types and rates of post-surgical complications associated with the Port Delivery System with ranibizumab (PDS) are comparable with those reported for other ocular implants that cross the sclera. METHODS: Systematic literature reviews were conducted to determine the long-term (≥ 18-month) safety of ocular implants that cross the sclera in clinical trials and real-world studies. Complication types and rates were compared with those reported for the PDS in phase III clinical trials (Archway, Pagoda, and Pavilion). RESULTS: Sixteen clinical trials (24 publications) and 43 real-world studies were identified reporting 30 complications in eyes with 15 implant types and 8 ocular diseases. Implants were associated with an acceptable, well-characterized safety profile, with most complications resolving spontaneously or with treatment. Device-related complications were reported in 0.7% (0.0-5.0%) of study eyes in clinical trials and 1.3% (0.0-14.5%) of eyes in real-world studies. Rates of conjunctival complications were 2.1% (0.0-22.8%) and 2.2% (0.9-4.6%), respectively. The overall types and rates of adverse events of special interest reported for the PDS in phase III trials (cataract, conjunctival bleb, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, endophthalmitis, implant dislocation, retinal detachment, and hyphema) were within the ranges reported for other ocular implants. CONCLUSIONS: The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera. This suggests that the long-term safety of the PDS is consistent with other ocular devices established in ophthalmology clinical practice. TRIAL REGISTRATION: PROSPERO international prospective register of systematic reviews: CRD5202234129, CRD42022343129.

Mild retinitis pigmentosa, including sector retinitis pigmentosa associated with 2 pathogenic variants in CDH23.

BACKGROUND: Biallelic pathogenic variants in CDH23 can cause Usher syndrome type I (USH1), typically characterized by sensorineural hearing loss, variable vestibular areflexia, and a progressive form of rod-cone dystrophy. While missense variants in CDH23 can cause DFNB12 deafness, other variants can affect the cadherin 23 function, more severely causing Usher syndrome type I D. The main purpose of our study is to describe the genotypes and phenotypes of patients with mild retinitis pigmentosa (RP), including sector RP with two pathogenic variants in CDH23. MATERIALS AND METHODS: Clinical examination included medical history, comprehensive ophthalmologic examination, and multimodal retinal imaging, and in case 1 and 2, full-field electroretinography (ERG). Genetic analysis was performed in all cases, and segregation testing of proband relatives was performed in case 1 and 3. RESULTS: Three unrelated cases presented with variable clinical phenotype for USH1 and were found to have two pathogenic variants in CDH23, with missense variant, c.5237 G > A: p.Arg1746Gln being common to all. All probands had mild to profound hearing loss. Case 1 and 3 had mild RP with mid peripheral and posterior pole sparing, while case 2 had sector RP. ERG results were consistent with the marked loss of retinal function in both eyes at the level of photoreceptor in case 1 and case 2, with normal peak time in the former. CONCLUSION: Patients harbouring c.5237 G > A: p.Arg1746Gln variants in CDH23 can present with a mild phenotype including sector RP. This can aid in better genetic counselling and in prognostication.

The Impact of the COVID-19 Pandemic on Tele-ophthalmology-Based Retinal Screening.

INTRODUCTION: This study reports our experiences with systematic retinal screening in Denmark through optometrists with access to tele-ophthalmological services before, during, and after the COVID-19 pandemic. METHODS: We evaluated an optometrist-based retinal screening system with a referral option for tele-ophthalmological service by a consultant ophthalmologist within the time period of August 1, 2018 to September 30, 2023. The optometrist collected patient history, refraction, best-corrected visual acuity, intraocular pressure, basic slit-lamp examination, 4-in-1 visual field report, and retinal imaging using color fundus 45° photography. Tele-ophthalmological services were provided by consultant ophthalmologists. Within pre-defined periods of pre-COVID-19, COVID-19, and post-COVID-19, we evaluated the rate of referrals to the tele-ophthalmological service, diagnoses made, and referrals to the public healthcare system. RESULTS: A total of 1,142,028 unique individuals, which corresponded to 19.1% of the entire population of Denmark, underwent screening by the optometrists; 50,612 (4.4%) of these individuals were referred to the tele-ophthalmological examination by consultant ophthalmologists. A referral for further ophthalmic examination, either at hospital or at an ophthalmic practice, was made for 10,300 individuals (20.4% of those referred for tele-ophthalmology, corresponding to 0.9% of the population screened). The referral rate from the screening to the tele-ophthalmological service increased from before COVID-19 (3.4%) to during COVID-19 (4.3%) and further after COVID-19 (6.4%). This increase coincided with an increasing prevalence of conditions seen in the tele-ophthalmological service. CONCLUSION: During a period of 5 years, 19.1% of the entire population of Denmark underwent retinal screening. This provided an adjunctive health service during a period of severe strain on the public healthcare system, while limiting the number of excessive referrals to the public healthcare system. Temporal trends illustrated an increased pattern of use of a large-scale tele-ophthalmological system.

Plasma Proteomics to Identify Drug Targets and Potential Drugs for Retinal Artery Occlusion: An Integrated Analysis in the UK Biobank.

Retinal artery occlusion (RAO), which is positively correlated with acute ischemic stroke (IS) and results in severe visual impairment, lacks effective intervention drugs. This study aims to perform integrated analysis using UK Biobank plasma proteome data of RAO and IS to identify potential targets and preventive drugs. A total of 7191 participants (22 RAO patients, 1457 IS patients, 8 individuals with both RAO and IS, and 5704 healthy age-gender-matched controls) were included in this study. Unique 1461 protein expression profiles of RAO, IS, and the combined data set, extracted from UK Biobank Plasma proteomics projects, were analyzed using both differential expression analysis and elastic network regression (Enet) methods to identify shared key proteins. Subsequent analyses, including single cell type expression assessment, pathway enrichment, and druggability analysis, were conducted for verifying shared key proteins and discovery of new drugs. Five proteins were found to be shared among the samples, with all of them showing upregulation. Notably, adhesion G-protein coupled receptor G1 (ADGRG1) exhibited high expression in glial cells of the brain and eye tissues. Gene set enrichment analysis revealed pathways associated with lipid metabolism and vascular regulation and inflammation. Druggability analysis unveiled 15 drug candidates targeting ADGRG1, which demonstrated protective effects against RAO, especially troglitazone (-8.5 kcal/mol). Our study identified novel risk proteins and therapeutic drugs associated with the rare disease RAO, providing valuable insights into potential intervention strategies.

Autophagy in drusen biogenesis secondary to age-related macular degeneration.

Age-related macular degeneration (AMD) is an emerging cause of blindness in aged people worldwide. One of the key signs of AMD is the degeneration of the retinal pigment epithelium (RPE), which is indispensable for the maintenance of the adjacent photoreceptors. Because of impaired energy metabolism resulting from constant light exposure, hypoxia, and oxidative stress, accumulation of drusen in AMD-affected eyes is observed. Drusen contain damaged cellular proteins, lipoprotein particles, lipids and carbohydrates and they are related to impaired protein clearance, inflammation, and extracellular matrix modification. When autophagy, a major cellular proteostasis pathway, is impaired, the accumulations of intracellular lipofuscin and extracellular drusen are detected. As these aggregates grow over time, they finally cause the disorganisation and destruction of the RPE and photoreceptors leading to visual loss. In this review, the role of autophagy in drusen biogenesis is discussed since impairment in removing cellular waste in RPE cells plays a key role in AMD progression. In the future, means which improve intracellular clearance might be of use in AMD therapy to slow the progression of drusen formation.

Effects of Hyperbaric Oxygen Therapy in the Treatment of Patients With Central Retinal Artery Occlusion: A Retrospective Study.

Background Central retinal artery occlusion (CRAO) results in sudden, painless vision loss. As an analogous condition to acute ischemic stroke, CRAO is an ophthalmological emergency, but a standardized treatment is lacking. Hyperbaric oxygen therapy (HBOT) has been widely used in spite of the inconsistent results reported. Purpose To report the visual acuity (VA) outcomes in all patients submitted to HBOT with non-arteritic CRAO in a tertiary center. Methods This retrospective study included all adult patients with CRAO and symptoms lasting for less than 24 hours who were prescribed HBOT in the Hyperbaric Medicine Unit of a Portuguese hospital from March 2009 to February 2023. Patient demographic information, medical history, ophthalmologic evaluation, hospital of referral, time until HBOT, supplementary treatments, number of HBOT sessions, adverse effects, and patient subjective VA gain were collected. All patients were subjected to 90-minute HBOT sessions with 100% oxygen at 2.4 ATA. The primary outcome was VA change (dif-logMAR) before and after treatment. A clinically significant visual improvement was defined as a dif-logMAR≥0.3. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2021; IBM Corp., Armonk, New York, United States) (p<0.05 is considered significant). Results A total of 114 patients were included in this study; 68% (n=77) were male, with a mean age of 69 years, and were subjected to a median number of seven HBOT sessions. No serious adverse effects from HBOT were reported. The mean time delay from symptoms to treatment was 12 hours, and best-corrected visual acuity (BCVA) at baseline was counting fingers or worse in 84% (n=96) of the patients. A dif-logMAR≥0.3 occurred in 46% (n=52) of the patients, and 58% (n=66) reported subjective VA improvement after the treatment. A significant improvement between BCVA before HBOT (2.12±0.74) and after HBOT (1.67±0.74) was observed. The VA outcome was found to be related to the total number of sessions, age, obesity, supplementary treatments, and cherry-red spot (CRS) at presentation. There were no significant effects of the time delay from symptoms to treatment in the explanation of the VA outcome. Conclusions HBOT appears to be safe and has a beneficial effect on VA outcomes in patients with non-arteritic CRAO, particularly depending on the number of sessions. Patient factors such as age, obesity, and the presence of CRSs also appear to influence the VA outcome.

Retinal debris triggers cytotoxic damage in cocultivated primary porcine RPE cells.

Introduction: One of the most common causes of vision loss in the elderly population worldwide is age-related macular degeneration (AMD). Subsequently, the number of people affected by AMD is estimated to reach approximately 288 million by the year 2040. The aim of this study was to develop an ex vivo model that simulates various aspects of the complex AMD pathogenesis. Methods: For this purpose, primary porcine retinal pigment epithelial cells (ppRPE) were isolated and cultured. One group was exposed to medium containing sodium iodate (NaIO3) to induce degeneration. The others were exposed to different supplemented media, such as bovine serum albumin (BSA), homogenized porcine retinas (HPR), or rod outer segments (ROOS) for eight days to promote retinal deposits. Then, these ppRPE cells were cocultured with porcine neuroretina explants for another eight days. To assess the viability of ppRPE cells, live/dead assay was performed at the end of the study. The positive RPE65 and ZO1 area was evaluated by immunocytochemistry and the expression of RLBP1, RPE65, and TJP1 was analyzed by RT-qPCR. Additionally, drusen (APOE), inflammation (ITGAM, IL6, IL8, NLRP3, TNF), oxidative stress (NFE2L2, SOD1, SOD2), and hypoxia (HIF1A) markers were investigated. The concentration of the inflammatory cytokines IL-6 and IL-8 was determined in medium supernatants from day 16 and 24 via ELISA. Results: Live/dead assay suggests that especially exposure to NaIO3 and HPR induced damage to ppRPE cells, leading in a significant ppRPE cell loss. All supplemented media resulted in decreased RPE-characteristic markers (RPE65; ZO-1) and gene expression like RLBP1 and RPE65 in the cultured ppRPE cells. Besides, some inflammatory, oxidative as well as hypoxic stress markers were altered in ppRPE cells cultivated with NaIO3. The application of HPR induced an enhanced APOE expression. Pre-exposure of the ppRPE cells led to a diminished number of cones in all supplemented media groups compared to controls. Discussion: Overall, this novel coculture model represents an interesting initial approach to incorporating deposits into coculture to mimic AMD pathogenesis. Nevertheless, the effects of the media used need to be investigated in further studies.

Effect of COVID-19 Shelter-In-Place Orders on Visual Outcomes of Ophthalmic Surgical Emergencies.

PURPOSE: To compare the outcomes of ophthalmic surgical emergencies during shelter-in-place (SIP) order with the corresponding period in 2019. METHODS: This retrospective cohort study compared patients presenting to the Bascom Palmer Eye Institute (BPEI) emergency department (ED) who underwent urgent surgery during the SIP period (March 23-May 17, 2020), compared to the same weeks in 2019 (non-SIP). Main outcome measures included symptom-to-ED time, ED-to-surgical decision time, surgical decision-to-operating room (OR) time, ED-to-OR time, and postoperative follow-up time. Secondary outcome measures included travel distance, visual acuity (VA), intraocular pressure (IOP), and number of glaucoma medications. RESULTS: Seventy-six and 148 patients presented with ophthalmic surgical emergencies in the SIP and non-SIP study periods, respectively. Retinal detachment (RD), acute glaucoma, and open globe injury were the most common diagnoses in both periods. Symptom-to-ED and surgical decision-to-OR times were shorter during the SIP period. SIP patients had comparable preoperative VA but worse postoperative VA compared to non-SIP patients. During the SIP period, RD patients experienced postoperative VA reduction rather than improvement (+0.09 vs. -0.23 logMAR, p = 0.03); glaucoma patients were less likely to reach surgical decision within 24 h (OR 0.16 [95% CI 0.03-0.95]); and globe injuries had longer ED-to-surgical decision time and ED-to-OR time compared to the non-SIP period. Other outcomes were similar between both study periods. CONCLUSION: There was reduced volume of ophthalmic surgical emergencies and worse postoperative vision during SIP compared to the non-SIP period, despite shorter symptom-to-ED and surgical decision-to-OR times suggesting minimal delays in seeking or receiving care.

FTIR study of light-induced proton transfer and Ca2+ binding in T82D mutant of TAT rhodopsin.

Proton transfer reactions play important functional roles in many proteins such as enzymes and transporters, which is also the case in rhodopsins. In fact, functional expression of rhodopsins accompanies intra-molecular proton transfer reactions in many cases. One of the exceptional cases can be seen in the protonated form of marine bacterial TAT rhodopsin, which isomerizes the retinal by light, but returns to the original state within 10-5 sec. Thus, light energy is converted into heat without any function. In contrast, the T82D mutant of TAT rhodopsin conducts the light-induced deprotonation of the Schiff base at high pH. In this paper, we report the structural analysis of T82D by means of difference FTIR spectroscopy. In the light-induced difference FTIR spectra at 77 K, we observed little HOOP vibrations for T82D as well as the wild type (WT), suggesting that the planar chromophore structure itself is not the origin of the reversion from the K intermediate in WT TAT rhodopsin. Upon relaxation of the K intermediate, T82D forms the following intermediate such as M, whereas K of WT returns to the original state. Present FTIR analysis revealed the proton transfer from the Schiff base to D82 in T82D upon formation of the M intermediate. It is accompanied the second proton transfer from E54 to the Schiff base, forming the N intermediate, particularly in membranes. The equilibrium between the M and N intermediates corresponds to the protonation equilibrium between E54 and the Schiff base. We also found that Ca2+ binding takes place in T82D as well as WT, but with 6-times lower affinity. Altered hydrogen-bonding network would be the origin of low affinity in T82D, where deprotonation of E54 is involved in the Ca2+ binding. (282 words).

Evaluation of Choroidal Thickness and Retinal Vessel Density with Serum HIF-1α and TNF-α Level in Patients with OSAS.

PURPOSE: To reveal changes in choroidal thickness, retinal vessel density, and serum HIF-1α and TNF-α levels in obstructive sleep apnea syndrome (OSAS) and their correlation. METHODS: This prospective case-control study included 118 patients divided into mild-to-moderate OSAS (n = 40), severe OSAS (n = 39), and a control group (n = 39). Choroidal thickness was evaluated with OCT, vessel density with OCTA, AHI index with polysomnography, and serum HIF-1α and TNF-α levels were analyzed using the enzyme-linked immunosorbent assay. RESULTS: The serum HIF-1α values of the participants in the mild-moderate OSAS and severe OSAS groups were [893.25(406.7-2068) and 1027(453-2527), respectively], and were both significantly higher than the control group [(521.5(231.6-2741))] (p < 0.001). Serum TNF-α levels did not differ significantly between the groups (p = 0.051).). Subfoveal choroidal thickness (SFCT) values of the severe OSAS groups were significantly lower than the control group (p < 0.05). The superficial and deep capillary plexus vascular density (SVD and DVD) values of the severe OSAS group were lower than the control group (p < 0.05). Serum HIF-1α and TNF-α levels of all participants were negatively correlated with both their SVD values (p < 0.05, r: -0.220 and p < 0.05, r: -0.252, respectively) and their DVD values (p < 0.001, r: -0.324 and p = 0.001, r: -0.299, respectively). CONCLUSIONS: Increased serum levels of inflammatory mediators (HIF-1α ve TNF-α) in OSAS cause a decrease in SFCT, SVD, and DVD, which is an indication of systemic vascular damage. Further research on developing treatment strategies to modulate TNF-α ve HIF-1α may help recede vascular morbidity in OSAS patients.

Evaluating the potential of retinal photography in chronic kidney disease detection: a review.

Background: Chronic kidney disease (CKD) is a significant global health concern, emphasizing the necessity of early detection to facilitate prompt clinical intervention. Leveraging the unique ability of the retina to offer insights into systemic vascular health, it emerges as an interesting, non-invasive option for early CKD detection. Integrating this approach with existing invasive methods could provide a comprehensive understanding of patient health, enhancing diagnostic accuracy and treatment effectiveness. Objectives: The purpose of this review is to critically assess the potential of retinal imaging to serve as a diagnostic tool for CKD detection based on retinal vascular changes. The review tracks the evolution from conventional manual evaluations to the latest state-of-the-art in deep learning. Survey Methodology: A comprehensive examination of the literature was carried out, using targeted database searches and a three-step methodology for article evaluation: identification, screening, and inclusion based on Prisma guidelines. Priority was given to unique and new research concerning the detection of CKD with retinal imaging. A total of 70 publications from 457 that were initially discovered satisfied our inclusion criteria and were thus subjected to analysis. Out of the 70 studies included, 35 investigated the correlation between diabetic retinopathy and CKD, 23 centered on the detection of CKD via retinal imaging, and four attempted to automate the detection through the combination of artificial intelligence and retinal imaging. Results: Significant retinal features such as arteriolar narrowing, venular widening, specific retinopathy markers (like microaneurysms, hemorrhages, and exudates), and changes in arteriovenous ratio (AVR) have shown strong correlations with CKD progression. We also found that the combination of deep learning with retinal imaging for CKD detection could provide a very promising pathway. Accordingly, leveraging retinal imaging through this technique is expected to enhance the precision and prognostic capacity of the CKD detection system, offering a non-invasive diagnostic alternative that could transform patient care practices. Conclusion: In summary, retinal imaging holds high potential as a diagnostic tool for CKD because it is non-invasive, facilitates early detection through observable microvascular changes, offers predictive insights into renal health, and, when paired with deep learning algorithms, enhances the accuracy and effectiveness of CKD screening.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Quantifying ocular microcirculation in hypertension patients with carotid artery stenosis.

Background: Carotid artery stenosis (CAS) is one of the most common macrovascular complications of hypertension. The ophthalmic artery springs from the internal carotid artery; however, the effect of CAS on ocular microcirculation has not been quantified in hypertension patients. This study aimed to quantify ocular microcirculation metrics in hypertension with CAS (HCAS) patients and to explore the relationship between micro- and macroangiopathy in hypertension. Methods: All participants (community-based) underwent detailed assessments, including carotid ultrasonography, optical coherence tomography angiography (OCTA), and enhanced depth imaging (EDI)-OCT. CAS was diagnosed using carotid ultrasonography. Retinal microcirculation metrics, including vessel density (VD), skeleton density (SD), fractal dimension (FD), and foveal avascular zone (FAZ), were quantified using OCTA and ImageJ software. Choroidal microcirculation metrics, including subfoveal choroidal thickness (SFCT), luminal area (LA), and choroidal vascularity index (CVI), were quantified using EDI-OCT and ImageJ. Retinal vessel caliber metrics, including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery/vein ratio (AVR), were calculated using revised formulas. The above metrics were compared among the HCAS group, hypertension with no CAS (HNCAS) group, and healthy control group. The mutual effects between ocular metrics and CAS were evaluated using regression analyses. Results: In a comparison of the HCAS vs. HNCAS groups, retinal metrics including VD, SD, FD, and choroidal metrics including CVI and LA were significantly decreased in the HCAS group (all p < 0.05); however, FAZ, SFCT, and retinal vessel caliber metrics including CRAE, CRVE, and AVR were comparable between groups (all p > 0.05). In a comparison of HNCAS and the healthy control group, VD, SD, and CRAE showed that AVR was significantly decreased in the HNCAS group (all p < 0.05); meanwhile, choroidal metrics were comparable between groups (all p > 0.05). Linear regression analyses showed that intima-media thickness (IMT) (p = 0.01) and peak systolic velocity (PSV) (p = 0.002) were negatively related to retinal VD in hypertension patients. Logistic regression analyses disclosed that older age (p < 0.001), smoking history (p = 0.002), lower VD (p = 0.04), SD (p = 0.02), and CVI (p < 0.001) were related to the presence of CAS in hypertension patients. Conclusion: CAS in hypertension-induced hypoperfusion in retinal and choroidal microcirculation and the decreased retinal VD and choroidal CVI were significantly associated with the presence of CAS in patients with hypertension, suggesting that hypertension macro- and microangiopathy were mutually affected and share the common pathophysiology. Furthermore, OCT could be a useful tool to assess hypertension patient's CAS risk profiles in a non-invasive way.

Retinal Vessel Functional Responses in South Africans Living With and Without HIV: The EndoAfrica-NWU Study.

OBJECTIVES: The effects of HIV and antiretroviral therapy (ART) on microvascular function are poorly explored. We compared retinal vessel functional responses to flicker light-induced provocation (FLIP) in people living with HIV (PLWH) and people living without HIV (PLWoutH). METHODS: We included 115 PLWH and 51 PLWoutH with a median age of 41 years. Treated PLWH received similar first-line fixed-dose combination ART. Clinical characteristics and retinal vessels functional responses to FLIP were compared in (a) PLWH and PLWoutH; and (b) PLWH groups stratified by the median of (i) CD4-count (511 cells/mm3), (ii) viral load (50 copies/mL), and (iii) ART duration (57.6 months). RESULTS: PLWH were older, smoked more, and had a lower prevalence of hypertension than PLWoutH (p < 0.05). Almost 64% of PLWH were infected for more than 5 years. Retinal vessel responses to FLIP were similar between PLWH and PLWoutH after taking confounders into account. In addition, PLWH subgroups stratified according to immuno-virological status by CD4-count, viral load, and ART duration showed no differences in retinal vessel responses to FLIP. CONCLUSION: Living with HIV and receiving ART were not associated with altered microvascular function as assessed with dynamic retinal vessel analysis in a South African case-control study.

Effect of Diurnal Light Conditions on Electroretinogram Responses to Red and Blue Flickering Light.

Bright light impacts the human circadian system such that exposure to bright light at night can suppress melatonin secretion, and exposure to bright light in the morning prevents light-induced melatonin suppression at night. The preventive effect of morning light may attenuate the prior history of light sensitivity of intrinsically photosensitive retinal ganglion cells (ipRGCs) that regulate the circadian system. In this study, we evaluated electroretinogram (ERG) responses to red and blue flickering lights following dim and bright daylight conditions. Eleven healthy females underwent ERG measurements during exposure to 33 Hz flickering red or blue light under dim and bright daytime conditions. We averaged ERG waves for 50 flickering light pulses of the trigger signal data. We obtained the amplitude of the signal-averaged ERG by calculating the difference between the waves' peaks and bottoms. Although there was no significant dim and bright light difference in the amplitude of ERG waves, the ERG amplitude to flickering blue light under the bright light condition was significantly lower than to flickering blue light under the dim light condition. In this study, blue light stimulated mainly ipRGCs and S-cones. Since S-cones may contribute minimally to the light-adapted 33 Hz flicker ERG results, our findings suggest that bright light during the daytime attenuates the sensitivity of human ipRGCs.

Reproducibility of SIMPLE classification for diabetic retinopathy screening and its comparison to current Italian guidelines.

PURPOSE: To evaluate the reproducibility of SIMPLE (Single field Image Multi Parameters defined Lesions Extent), a new Diabetic Retinopathy (DR) classification for screening of 45° single field fundus pictures of patients with diabetes (PwDM), assessing DR, Diabetic Maculopathy (DMac) and referral rate agreement and comparing it to current Italian Guidelines (IG). MATERIALS AND METHODS: We conducted a retrospective, observational, multicentre study, collecting 1000 retinal 45° single field images of PwDM obtained during routine visits in two diabetes clinics. Three ophthalmologists evaluated each image, determining the presence and number of specific DR lesions and then assigning a stage according to the current IG for screening. SIMPLE staging was performed automatically via Excel software, based on the pre-specified DR characteristics observed by the graders. We analysed intra-centre, inter-centre and total inter-grader agreement for DR and DMac stage and referral rate of the two classifications. RESULTS: Agreement amongst the three graders was consistently higher when using SIMPLE classification than when using current IG classification. For DR, kappa (k) was 0.86 with IG and 0.95 with SIMPLE classification; for DMac, k-IG was 0.78, while k-SIMPLE was 0.96; concordance on the referral rate was 0.91 with IG and 0.99 with SIMPLE. Similar results were obtained in sub-analyses for the evaluation of intra-centre and inter-centre concordance. CONCLUSIONS: Our results suggest that the new SIMPLE classification has an excellent reproducibility amongst graders, comparable or superior to the current IG for DR screening proposed in 2015, improving the standardisation of the decision on referability.

Retinal layer thinning for monitoring disease-modifying treatment in relapsing multiple sclerosis-Evidence for applying a rebaselining concept.

BACKGROUND: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT). METHODS: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6-12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFLbaseline/aLpRNFLrebaseline) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPLbaseline/aLGCIPLrebaseline) by mixed-effects linear regression models. RESULTS: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFLbaseline and aLGCIPLbaseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFLrebaseline nor aLGCIPLrebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFLrebaseline (by 0.31%, p < 0.001) and aLGCIPLrebaseline (0.25%, p < 0.001) compared with M-DMT. CONCLUSIONS: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity.