Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

RETINAL AND VITREOUS CHANGES ASSOCIATED WITH SPONTANEOUS IMPROVEMENT IN MYOPIC MACULAR SCHISIS.

PURPOSE: To describe the retinal and vitreous changes in eyes showing myopic macular schisis (MMS) improvement when vitrectomy was not performed and identify triggering factors. DESIGN: Retrospective observational study. SUBJECTS: Patients with non-operated myopic macular schisis METHODS: The records of patients with MMS who were followed without performing surgery for more than 6 months were retrospectively reviewed, and the eyes showing an anatomical improvement were included. MMS evolution was analyzed quantitatively (central foveal thickness [CFT], parafoveal thickness, maximum height) and qualitatively (presence/absence of foveal detachment, lamellar hole, epiretinal membrane, choroidal neovascularization, inner and outer retinoschisis, vitreous status) at baseline and at the final visit. An anatomical improvement was defined as a decrease in CFT by at least 50 µm. MAIN OUTCOME MEASURE: The rate anatomical improvement of MMS without performing vitrectomy and the morphological changes observed in these cases. RESULTS: In a cohort of 74 non-operated eyes with MMS, MMS improved in 14 eyes (19%) after a mean follow-up of 55 ± 38 months (range: 8-138). In these improved cases, the mean decrease in CFT was 153 ± 166 µm (range: 24-635, p=0.005) and a complete resolution of MMS was observed in 9 eyes (64%). In 9 eyes (64%), the improvement was associated with visible vitreous changes in the macular area on the OCT scans. The mean visual acuity, which was already good at baseline (20/50, 0.4 ± 0.2 LogMAR), increased at the last visit (20/40, 0.3 ± 0.3 LogMAR) but without reaching significance. CONCLUSION: This long-term follow-up analysis showed that almost 20% of MMS in eyes without indication for surgery could improve over time. In most cases, the improvement was associated with an apparent resolution of vitreous tensions.

Spatially resolved imaging of human macular capillaries using adaptive optics-enhanced optical coherence tomography angiography.

Documenting the organization of the retinal capillaries is of importance to understand the visual consequences of vascular diseases which may differentially affect the microvascular layers. Here we detailed the spatial organization of the macular capillaries in ten healthy human subjects using a prototypic adaptive optics-enhanced optical coherence tomography angiography (AO-OCTA) system. Within the central 6° × 6°, the radial peripapillary capillaries and the superficial, intermediate and deep vascular plexuses (SVP, IVP and DVP, respectively) were consistently resolved. In 8 out of the 10 eyes, the capillary segments composing the perifoveal arcade (PFA) were perfused only by the SVP, while drainage of the PFA showed more variability, comprising a case in which the PFA was drained by the DVP. Around the center, a distinct central avascular zone could be documented for each layer in 7 of the 10 cases; in three eyes, the IVP and SVP merged tangentially around the center. In all eyes, the foveal avascular zone was larger in the DVP than in the SVP and IVP. In one eye with incomplete separation of the inner foveal layers, there was continuity of both the SVP and the IVP; a central avascular zone was only present in the DVP. The diversity of perfusion and drainage patterns supported a connectivity scheme combining parallel and serial organizations, the latter being the most commonly observed in perifoveal vessels. Our results thus help to further characterize the diversity of organization patterns of the macular capillaries and to robustly analyze the IVP, which will help to characterize early stages of microvascular diseases.

Methotrexate versus conventional disease-modifying antirheumatic drugs in the treatment of non-anterior sarcoidosis-associated uveitis.

AIMS: To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis. METHODS: Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation. RESULTS: 58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 -not reached) vs 8.4 months (3.1-22.9) with MMF and 16.8 months (8.0-90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively. CONCLUSION: In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile.

Neuroretinal Alterations in Schizophrenia and Bipolar Disorder: An Updated Meta-analysis.

Schizophrenia (SZ) and bipolar disorder (BD) are characterized by major symptomatic, cognitive, and neuroanatomical changes. Recent studies have used optical coherence tomography (OCT) to investigate retinal changes in SZ and BD, but their unique and shared changes require further evaluation. Articles were identified using PubMed and Google Scholar. 39 studies met the inclusion criteria. Diagnostic groups were proband (SZ/BD combined), SZ, BD, and healthy control (HC) eyes. Meta-analyses utilized fixed and random effects models when appropriate, and publication bias was corrected using trim-and-fill analysis ("meta" package in R). Results are reported as standardized mean differences with 95% CIs. Data from 3145 patient eyes (1956 SZ, 1189 BD) and 3135 HC eyes were included. Studies identified thinning of the peripapillary retinal nerve fiber layer (pRNFL, overall and in 2 subregions), m-Retina (overall and all subregions), mGCL-IPL, mIPL, and mRPE in SZ patients. BD showed thinning of the pRNFL (overall and in each subregion), pGCC, and macular Retina (in 5 subregions), but no changes in thickness or volume for the total retina. Neither SZ nor BD patients demonstrated significant changes in the fovea, mRNFL, mGCL, mGCC, mINL, mOPL, mONL, or choroid thicknesses. Moderating effects of age, illness duration, and smoking on retinal structures were identified. This meta-analysis builds upon previous literature in this field by incorporating recent OCT studies and examining both peripapillary and macular retinal regions with respect to psychotic disorders. Overall, this meta-analysis demonstrated both peripapillary and macular structural retinal abnormalities in people with SZ or BD compared with HCs.

The impact of intraocular pressure on optical coherence tomography angiography: A review of current evidence.

A scoping review of 45 peer-reviewed manuscripts involving intraocular pressure (IOP) change and concurrent optical coherence tomography angiography (OCTA) assessments was performed to aggregate knowledge, summarize major findings, and identify gaps in literature and methodology relating to the effect of IOP change on OCTA. Articles were identified through PubMed/Medline, Google Scholar, Cochrane, Web of Science, and article reference lists. A total of 838 results were identified, and 45 articles met the inclusion and exclusion criteria for detailed analysis. OCTA metrics including vessel density (VD), perfusion density, and flow density of the superficial capillary plexus and the radial peripapillary capillaries were analyzed in relation to relative temporal IOP changes. Overall, IOP changes were found to affect superficial vascular plexus (VD) measurements on OCTA, especially when IOP elevated above the physiologic normal range (10-21 mmHg). No significant association was found between diurnal IOP variation and OCTA metrics. Cataract surgery improved the whole-image signal strength and VD regardless of changes in IOP. Beta-blockers were associated with paradoxically reduced vessel density in normal tension glaucoma patients in two studies. Although glaucoma surgical intervention studies were inconsistent and limited by scan quality and low sample sizes, patients requiring glaucoma surgery exhibited attenuated postoperative superficial VD recovery despite significant IOP reductions with surgical intervention. In addition to ensuring near-perfect signal strength with minimal media opacities and controlling for high myopia, central corneal thickness, and the presence of retinopathy, clinicians should consider the statistically significant impact of IOP on OCTA metrics when interpreting results.

Aging of the eye: Lessons from cataracts and age-related macular degeneration.

Aging is the greatest risk factor for chronic human diseases, including many eye diseases. Geroscience aims to understand the effects of the aging process on these diseases, including the genetic, molecular, and cellular mechanisms that underlie the increased risk of disease over the lifetime. Understanding of the aging eye increases general knowledge of the cellular physiology impacted by aging processes at various biological extremes. Two major diseases, age-related cataract and age-related macular degeneration (AMD) are caused by dysfunction of the lens and retina, respectively. Lens transparency and light refraction are mediated by lens fiber cells lacking nuclei and other organelles, which provides a unique opportunity to study a single aging hallmark, i.e., loss of proteostasis, within an environment of limited metabolism. In AMD, local dysfunction of the photoreceptors/retinal pigmented epithelium/Bruch's membrane/choriocapillaris complex in the macula leads to the loss of photoreceptors and eventually loss of central vision, and is driven by nearly all the hallmarks of aging and shares features with Alzheimer's disease, Parkinson's disease, cardiovascular disease, and diabetes. The aging eye can function as a model for studying basic mechanisms of aging and, vice versa, well-defined hallmarks of aging can be used as tools to understand age-related eye disease.

Bilateral peripapillary choroidal neovascular membranes in Vogt-Koyanagi-Harada disease.

Choroidal neovascular membrane (CNVM) in Vogt-Koyanagi-Harada disease (VKH) is a known entity, observed primarily during the chronic convalescent and chronic-recurrent phases of the disease. However, the peripapillary location of CNVM is a rare finding.We describe a case of chronic VKH with bilateral peripapillary CNVM detected using multimodal imaging and the associated differential diagnoses and treatment approach.A combination of anti-vascular endothelial growth factor injections, systemic steroids and immunosuppressants is often required to manage the aggressive course of this choroidal neovascularisation.

Prevalence and Risk Factors for Metamorphopsia after Successful Retinal Detachment Surgery.

INTRODUCTION: The aim of the study was to determine the prevalence of metamorphopsia following rhegmatogenous retinal detachment (RRD) surgery, as well as associated predictive factors. METHODS: A total of 107 eyes successfully operated for RRD underwent metamorphopsia severity assessment using M-CHARTS, and foveal microstructure analysis by spectral domain optical coherence tomography, at 1 and 6 months postoperatively. Univariate and multivariate logistic regression rendered evaluation of preoperative risk factors. The correlation between metamorphopsia score and outer retinal layer (ORL) integrity was investigated and preoperative risk factors evaluated. RESULTS: The prevalence of postoperative metamorphopsia decreased from 51.4 to 29.9% and the median metamorphopsia score significantly improved (0.5, 95% CI: 0.3; 0.9, to 0.2, 95% CI: 0; 0.5, p < 0.001) from 1 to 6 months, respectively. Preoperative macular detachment was the only predictor found (OR 11.0, 95% CI: 3.1; 39.4, p < 0.001). Metamorphopsia severity was significantly associated with outer nuclear layer thickness and the status of the ellipsoid and cone interdigitation zones. One-month M-CHARTS had 81% sensitivity and 87% specificity in predicting full metamorphopsia recovery at 6 months (0.45 cut-off score). CONCLUSION: The prevalence of metamorphopsia decreased in parallel to ORL restoration, thus demonstrating the etiological role of photoreceptor-level morphological changes. M-CHARTS allowed for monitoring and predicting metamorphopsia recovery after RRD.

Differential gene expression between central and peripheral retinal regions in dogs and comparison with humans.

The dog retina contains a central macula-like region, and there are reports of central retinal disorders in dogs with shared genetic etiologies with humans. Defining central/peripheral gene expression profiles may provide insight into the suitability of dogs as models for human disorders. We determined central/peripheral posterior eye gene expression profiles in dogs and interrogated inherited retinal and macular disease-associated genes for differential expression between central and peripheral regions. Bulk tissue RNA sequencing was performed on 8 mm samples of the dog central and superior peripheral regions, sampling retina and retinal pigmented epithelium/choroid separately. Reads were mapped to CanFam3.1, read counts were analyzed to determine significantly differentially expressed genes (DEGs). A similar analytic pipeline was used with a published bulk-tissue RNA sequencing human dataset. Pathways and processes involved in significantly DEGs were identified (Database for Annotation, Visualization and Integrated Discovery). Dogs and humans shared the extent and direction of central retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. Many genes implicated in heritable retinal disorders in dogs and humans were differentially expressed between central and periphery. Approximately half of genes associated with human age-related macular degeneration were differentially expressed in human and dog tissues. We have identified similarities and differences in central/peripheral gene expression profiles between dogs and humans which can be applied to further define the relevance of dogs as models for human retinal disorders.

Pros and cons of internal limiting membrane peeling during epiretinal membrane surgery: a randomised clinical trial with microperimetry (PEELING).

BACKGROUND: After idiopathic epiretinal membrane (iERM) removal, it is unclear whether the internal limiting membrane (ILM) should be removed. The objective was to assess if active ILM peeling after iERM removal could induce microscotomas. METHODS: The PEELING study is a national randomised clinical trial. When no spontaneous ILM peeling occurred, patients were randomised either to the ILM peeling or no ILM peeling group. Groups were compared at the month 1 (M1), M6 and M12 visits in terms of microperimetry, best-corrected visual acuity (BCVA) and optical coherence tomography findings. The primary outcome was the difference in microscotoma number between baseline and M6. RESULTS: 213 patients were included, 101 experienced spontaneous ILM peeling and 100 were randomised to the ILM peeling (n=51) or no ILM peeling group (n=49). The difference in microscotoma number between both groups was significant at M1 (3.9 more microscotomas in ILM peeling group, (0.8;7.0) p=0.0155) but not at M6 (2.1 more microscotomas in ILM peeling group (-0.5;4.7) p=0.1155). Only in the no ILM peeling group, the number of microscotomas significantly decreased and the mean retinal sensitivity significantly improved. The ERM recurred in nine patients in the no ILM peeling group (19.6%) versus zero in the ILM peeling group (p=0.0008): two of them underwent revision surgery. There was no difference in mean BCVA and microperimetry between patients experiencing or not a recurrence at M12. CONCLUSION: Spontaneous ILM peeling is very common. Active ILM peeling prevents anatomical ERM recurrence but may induce retinal impairments and delay visual recovery. TRIAL REGISTRATION: NCT02146144.

[Morphological features of an optic nerve in premature infants according to the optical coherence tomography data]. / Morfologicheskie osobennosti zritel'nogo nerva u nedonoshennykh detei po dannym opticheskoi kogerentnoi tomografii.

OBJECTIVE: To assess the morphological state of the visual analyzer in premature infants in long-term. MATERIAL AND METHODS: We examined 40 premature children (74 eyes) aged 10.3±2.92 years (gestational age (GA) 25-34 weeks, birth weight (BW) 690-2700 g). Twenty mature children (40 eyes), aged 10.8±3.05 years, were examined as a control group. The children underwent standard ophthalmologic examination, optical coherence tomography (OCT) and recording of visual evoked potentials (VEP). RESULTS: The thickness of retinal nerve fiber layer (RNFL) is less in preterm infants than in term infants, regardless of retinopathy of prematurity (ROP) and refraction (p<0.05). Thickness loss has an inverse proportion with the degree of hypoxic-ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH) (p<0.05). Retinal thickness in fovea is significantly greater in preterm infants and has a direct proportionality with the degree of IVH and the number of days on artificial lung ventilation (p<0.05). Moderate organic changes were detected in conduction pathways in 43.08% of premature infants according to VEP data. CONCLUSION: The use of OCT and recording of VEP may improve the quality of comprehensive neuro-ophthalmologic diagnosis in preterm infants. The thickness loss of RNFL can be expected in premature infants with HIE and IVH.

Acute macular neuroretinopathy following Valsalva manoeuvre: an insight into the pathophysiology.

Acute macular neuroretinopathy (AMN) affects the outer retina and is most likely induced by non-inflammatory ischaemia of the retinal deep capillary plexus and choriocapillaris. A man in his early 20s developed Valsalva retinopathy following weightlifting at the gym and presented with blurring of vision in the left eye 1 month after the initial retinal haemorrhages had resolved. A diffuse, purplish, donut-shaped, perifoveal lesion was seen on funduscopy and was well defined by an optical coherence tomography angiography (OCTA) en face image in the left eye. Outer retinal changes on optical coherence tomography (OCT) and a dense co-localised scotoma on a visual field (VF) examination confirmed the diagnosis of AMN, and the patient was started on a tapering dose of oral steroids. Improvement was seen in OCT, OCTA and VF during the 6-month follow-up visit. The use of OCTA en face imaging enabled the accurate identification of the lesion in the affected layers of the retina.

Foveal atrophy in patients with active central serous chorioretinopathy at first presentation: characteristics and treatment outcomes.

BACKGROUND/AIMS: This study aimed to investigate the clinical characteristics and treatment outcomes of patients with active central serous chorioretinopathy (CSC) and foveal atrophy. METHODS: Patients diagnosed with active idiopathic CSC using multimodal imaging and followed up for at least 6 months were included. They were divided into two groups (foveal atrophy group vs foveal non-atrophy group) according to a cut-off central foveal thickness of 120 µm on baseline optical coherence tomography (OCT). Baseline characteristics, angiographic and tomographic features and treatment outcomes were compared between the two groups. RESULTS: Of the 463 patients, 92 eyes of 92 patients (19.9%) were in the foveal atrophy group and 371 eyes of 371 patients (80.1%) were in the foveal non-atrophy group. The baseline subretinal fluid (SRF) height was 111.3±76.8 µm in the foveal atrophy group and 205.0±104.4 µm in the foveal non-atrophy group on OCT images (p<0.001). Complete resolution of SRF after treatment was noted in 60.4% and 93.5% of patients in the foveal atrophy and foveal non-atrophy groups at the final visit, respectively (p<0.001). The foveal atrophy group showed worse visual acuity at baseline (logarithm of the minimum angle of resolution, 0.43±0.33 vs 0.13±0.18, p<0.001) and final visit (0.41±0.32 vs 0.05±0.15, p=0.035). CONCLUSIONS: CSC with foveal atrophy was associated with a shallow SRF height, low treatment efficacy and poor vision before and after treatment. We suggest that early active treatment should be considered for eyes with CSC accompanied by a persistent shallow SRF and foveal atrophy.

Atypical Presentation Revealing Sorsby Macular Dystrophy: A Case Report.

Sorsby macular dystrophy is an autosomal dominant disorder secondary to heterozygous mutations in the TIMP3 gene in 22q12. It begins with fine, pale, drusen-like deposits or confluent, faint yellow material or sheets beneath the retinal pigment epithelium, but it eventually progresses to either geographic atrophy with pigmentary clumps or scars due to the choroidal neovascular membrane around the fourth decade of life. We describe a patient who presented with a progressive loss of unilateral visual acuity, wrongly suggesting an infectious or inflammatory disease.

Comparing generative and retrieval-based chatbots in answering patient questions regarding age-related macular degeneration and diabetic retinopathy.

BACKGROUND/AIMS: To compare the performance of generative versus retrieval-based chatbots in answering patient inquiries regarding age-related macular degeneration (AMD) and diabetic retinopathy (DR). METHODS: We evaluated four chatbots: generative models (ChatGPT-4, ChatGPT-3.5 and Google Bard) and a retrieval-based model (OcularBERT) in a cross-sectional study. Their response accuracy to 45 questions (15 AMD, 15 DR and 15 others) was evaluated and compared. Three masked retinal specialists graded the responses using a three-point Likert scale: either 2 (good, error-free), 1 (borderline) or 0 (poor with significant inaccuracies). The scores were aggregated, ranging from 0 to 6. Based on majority consensus among the graders, the responses were also classified as 'Good', 'Borderline' or 'Poor' quality. RESULTS: Overall, ChatGPT-4 and ChatGPT-3.5 outperformed the other chatbots, both achieving median scores (IQR) of 6 (1), compared with 4.5 (2) in Google Bard, and 2 (1) in OcularBERT (all p ≤8.4×10-3). Based on the consensus approach, 83.3% of ChatGPT-4's responses and 86.7% of ChatGPT-3.5's were rated as 'Good', surpassing Google Bard (50%) and OcularBERT (10%) (all p ≤1.4×10-2). ChatGPT-4 and ChatGPT-3.5 had no 'Poor' rated responses. Google Bard produced 6.7% Poor responses, and OcularBERT produced 20%. Across question types, ChatGPT-4 outperformed Google Bard only for AMD, and ChatGPT-3.5 outperformed Google Bard for DR and others. CONCLUSION: ChatGPT-4 and ChatGPT-3.5 demonstrated superior performance, followed by Google Bard and OcularBERT. Generative chatbots are potentially capable of answering domain-specific questions outside their original training. Further validation studies are still required prior to real-world implementation.

Clinical features of patients with mutations in genes for nanophthalmos.

BACKGROUND/AIMS: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 (PRSS56), membrane-type frizzled-related protein (MFRP), myelin regulatory factor (MYRF) and transmembrane protein 98 (TMEM98) and to evaluate the association between angle-closure glaucoma (ACG) and NNO. METHODS: Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis. RESULTS: Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP. Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma. CONCLUSION: Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling.