Fluorescein Angiography of Floating Retinal Veins.

This case report describes a diagnosis of floating retinal veins in a patient aged 4 years with a history of stage 2 familial exudative vitreoretinopathy.

Retinal artery to vein ratio is associated with cerebral microbleeds in individuals with type 1 diabetes.

OBJECTIVES: A third of asymptomatic individuals with type 1 diabetes (T1D) show signs of cerebrovascular disease in brain MRI. These signs associate with advanced stages of diabetic retinal disease, but not in mild or moderate retinopathy. We aimed to evaluate a wider spectrum of retinal changes by exploring the relationship between quantitative measures of retinal vessel parameters (RVP) and cerebrovascular changes in T1D. METHODS: We included 146 neurologically asymptomatic individuals with T1D [51% women, median age 40 (33.0-45.1) years] and 24 healthy, sex-matched and age-matched controls. All individuals underwent a clinical and biochemical work-up and brain MRI, which was evaluated for cerebral microbleeds (CMBs), white matter hyperintensities, and lacunar infarcts. RVPs, including central retinal arteriole (CRAE) and central retinal vein (CRVE) equivalents and the ratio of the two variables (arteriovenous ratio, AVR) were assessed quantitatively by a computer-assisted method (IVAN software, version 3.2.6) from fundus images. RESULTS: Among T1D participants, those with CMBs had a lower arteriovenous ratio (AVR) compared with those without CMBs ( P  = 0.023). AVR was inversely associated with the amount of CMBs ( r  = -0.063, P  = 0.035). CMB prevalence was higher in those with AVR below the median (31%) compared with above the median (16%, P  < 0.001), and this difference was significant also after individuals with only no-to-mild retinopathy were included (28 vs. 16%, P  = 0.005). A correlation between blood pressure and CRAE ( r  = -0.19, P  = 0.025) appeared among those with T1D. CONCLUSION: Regardless of the severity of diabetic retinopathy, AVR is associated with the existence of CMBs in T1D.

Hemi-retinal vein occlusion: Characterizing a rare retinal vasculopathy.

PURPOSE: To characterize hemi-retinal vein occlusion (HRVO) in patients presenting to a multi-tier ophthalmology hospital network. METHODS: This retrospective, hospital-based study analyzed 2,834,616 new patients between August 2010 and June 2021. Patients with a clinical diagnosis of HRVO in at least one eye were included as cases. Data were collected using an electronic medical record system. Data were compared to the findings noted in branch RVO (BRVO) and central RVO (CRVO) patients. RESULTS: HRVO constituted 0.9% ( n = 191) of all the retinal vein occlusions (RVOs), with the mean age being 60.55 ± 10.14 years. Most patients were male (125, 65.45%) with unilateral (92.67%) affliction. Majority presented during the sixth (31.41%) or seventh (32.46%) decade of life. Most patients reported mild (37.07%) or moderate (27.32%) visual impairment, with vision < 20/200 being less common in HRVO (25.8%) and BRVO (17.2%) compared to CRVO (44.1%) ( P < 0.00001). Glaucoma was diagnosed and treated in 49 (23.90%) eyes, which was much higher than CRVO (11.45%) and BRVO (5.04%) ( P < 0.001), though neovascular glaucoma was much less than CRVO (2.9% vs. 9.2%) ( P = 0.0037). On follow-up, HRVO eyes (12.2%) had lesser vision loss compared to CRVO eyes (13.7%) (this difference does not look very significant to me), though BRVO had the least (9.1%) vision loss. CONCLUSION: HRVO is a rare RVO, presenting more in males. It causes less-severe visual impairment compared to CRVO. Large majority of patients with HRVO do not have identifiable systemic risk factors other than age. Preexisting glaucoma was more associated with HRVO compared to other RVOs.

Atrofia coriorretiniana pigmentada paravenosa de presentación unifocal y unilateral / Unifocal and unilateral pigmented paravenous retinochoroidal atrophy

La atrofia coriorretiniana pigmentada paravenosa es una entidad infrecuente, asociada a enfermedades autoinmunes y otras complicaciones oculares, generalmente multifocal, bilateral y simétrica. Se presenta el caso clínico de una paciente con artritis reumatoide que acude por dolor de varios días. Presenta disminución de agudeza visual de ojo izquierdo, escleritis nodular y atrofia coriorretiniana con acumulación de pigmento en espículas óseas en arcada vascular temporal inferior y agujero macular lamelar. El ojo derecho no presenta alteraciones. La autofluorescencia del ojo izquierdo muestra hipoautofluorescencia de bordes definidos en la lesión. La angiografía con fluoresceína evidencia hiperfluorescencia compatible con degeneración del epitelio pigmentario retiniano y bloqueo en las áreas de pigmento. El campo visual revela un defecto altitudinal en hemicampo superior. Este caso describe una atrofia coriorretiniana pigmentada paravenosa atípica unifocal y unilateral. Se debe conocer esta variante para realizar un correcto diagnóstico diferencial, así como proporcionar una información pronóstica adecuada (AU)

Paravenous pigmented chorioretinal atrophy is a generally multifocal, bilateral and symmetric rare entity associated with autoimmune diseases and other ocular complications. We present the clinical case of a patient with rheumatoid arthritis who attended for pain of several days. He presented decreased visual acuity of the left eye, nodular scleritis and chorioretinal atrophy with pigment accumulation in bone spicules in the inferior temporal vascular arcade and lamellar macular hole. The right eye shows no alterations. LE autofluorescence shows a hypoautofluorescence lesion with defined edges. Fluorescein angiography shows hyperfluorescence consistent with retinal pigmentary epithelial degeneration and blockage in pigment areas. The visual field reveals a defect in the superior hemifield. This case describes an atypical unifocal and unilateral paravenous pigmented chorioretinal atrophy. This variant must be known to make a correct differential diagnosis, as well as to provide adequate prognostic information (AU)

Direct ophthalmoscopy as a screening tool to study retinal vascular changes in acute mountain sickness in response to recent ascent to high altitude: A pilot study.

Background Advanced diagnostics are not easily accessible in austere topographical locations. We documented retinal changes in patients with acute mountain sickness (AMS+) and compared these with asymptomatic individuals (AMS-) with recent induction into high altitude using direct ophthalmoscopy as a screening tool. Methods We evaluated 97 individuals (43 AMS- and 54 AMS+) who were inducted to an altitude 3800 m above sea level by direct ophthalmoscopy after pupillary dilatation, on day 2 of arrival. Results Retinal vein dilatation was seen in 36 (66.7%) AMS+ v. 14 (32.6%) AMS- (p<0.01), hyperaemia of the optic disc in 30 (55.6%) AMS+ v. 14 (32.6%) AMS- (p<0.05), hyperaemia of the optic disc along with retinal vein dilatation in 27 (50%) AMS+ v. 9 (20.9%) AMS- (p<0.01), retinal vein tortuosity in 12 (22.2%) AMS+ v. 3 (7%) AMS- (p<0.02). In AMS+ with retinal vein dilatation 17 (50%) had SpO2 >91% and 19 (79.2%) had SpO2 <91% (p<0.01). An AMS score of >5 was recorded in 25 (69.4%; p<0.001) with venular dilatation and in 19 (52.8%; p<0.001) who were AMS+ with an induction number ≥3 had retinal dilatation. Conclusion Acute hypobaric hypoxia causes retinal venous dilatation, tortuosity and hyperaemia of the optic disc in those with AMS and correlates directly with SpO2 levels. The incidence of retinal vein dilatation increases with frequent re-entry into high altitude and more severe symptoms of AMS. Hence, all those being inducted to high altitude should be screened for retinal vascular changes.

Combined central retinal vein and cilioretinal artery occlusion in a 25-year-old woman.

We report a case of a 25-year-old woman with sudden and painless diminution in vision and central scotoma in her left eye (LE). She was a smoker and had been taking combined oral contraceptive (COC) pills for 1 year. On admission, the best-corrected visual acuity (BCVA) was 1,5/50 in the LE. Posterior segment examination revealed optic disc edema with flame-shaped retinal hemorrhages, mildly tortuous and dilated retinal veins. Moreover, retinal edema in the peripapillary and perimacular region, foci of hemorrhages and Roth's spots in the posterior pole, as well as pale superior papillomacular bundle were observed. Fundus fluorescein angiography (FFA) confirmed the delayed flow of contrast through the cilioretinal artery in the LE. The clinical picture suggested left central retinal vein (CRVO) with cilioretinal artery occlusion (CLRAO). All laboratory and imaging tests were normal except for homozygous methylenetetrahydrofolate reductase (MTHFR) gene mutation (A1298C genotypes). However, serum homocysteine (Hcy) level was normal. Low molecular weight heparin (LMWH) treatment was administered. Retinal lesions, as well as BCVA improved, but central scotoma remained. Abbreviations: aPTT = activated partial thromboplastin time, BCVA = best-corrected visual acuity, CBC = complete blood count, CLRAO = cilioretinal artery occlusion, COC = combined oral contraceptive, CRA = central retinal artery, CRP = serum C-reactive protein, CRVO = central retinal vein occlusion, CT = computed tomography, CTA = computed tomography angiography, ECG = electrocardiography, ESR = erythrocyte sedimentation rate, FERG = flash electroretinogram, FFA = fundus fluorescein angiography, GCA = ganglion cell analysis, GCL = ganglion cell layer, Hcy = homocysteine, ICGA = indocyanine green angiography, INR = international normalized ratio, IOP = intraocular pressure, IPL = inner plexiform layer, LE = left eye, LMWH = low molecular weight heparin, mfERG = multifocal electroretinogram, MTHFR = methylenetetrahydrofolate reductase, OCT = optical coherence tomography, RE = right eye, VF = visual field.

ASSOCIATION OF PIGMENTED PARAVENOUS RETINOCHOROIDAL ATROPHY WITH A PATHOGENIC VARIANT IN THE HK1 GENE.

PURPOSE: To report a case of pigmented paravenous retinochoroidal atrophy in a patient that was found to have an autosomal dominant pathogenic variant of the hexokinase 1 ( HK1 ) gene. METHODS: A case report. RESULTS: A 41-year-old White woman with a distant family history of retinitis pigmentosa presented with a 5-year history of bilateral blurry and decreased vision that led to eventual loss of ability to drive. Color funduscopic photographs revealed retinochoroidal atrophy, hyper-reflective spots within the retina, and a paravenous distribution of pigment bilaterally. Given the patient's familial ocular history and workup, she was diagnosed with inherited retinal degeneration with phenotype suggestive of pigmented paravenous retinochoroidal atrophy. Genetic testing revealed a single rare variant, c.2551 G>A in the HK1 gene. DISCUSSION: This case describes a pathogenic variant in HK1 , a gene that has been associated with RP, but has not been previously reported in association with the pigmented paravenous retinochoroidal atrophy phenotype. This expands the phenotypes associated with HK1 pathogenic variant, p.Glu851Lys, and the genetic association of pigmented paravenous retinochoroidal atrophy to include HK1 . Although pigmented paravenous retinochoroidal atrophy has been previously reported to be associated with CRB1 gene, no previous relationship to the HK1 gene has been described.

Retinal Venular Tortuosity Jointly with Retinal Amyloid Burden Correlates with Verbal Memory Loss: A Pilot Study.

INTRODUCTION: Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. METHODS: We used quantitative RFI in a cohort of patients with cognitive impairment to automatically compute retinal amyloid burden. Retinal blood vessels were segmented, and the vessel tortuosity index (VTI), inflection index, and branching angle were quantified. We assessed the correlations between retinal vascular and amyloid parameters, and cognitive domain Z-scores using linear regression models. RESULTS: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. Eleven subjects had normal cognition and 18 had impaired cognition. Retinal VTI was discriminated among cognitive scores. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs. 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory Scale-IV and SF-36 mental component score Z-scores (p < 0.05). CONCLUSION: This pilot study showed that retinal venular VTI combined with the proximal mid-periphery amyloid count could predict verbal memory loss. Future research is needed to finesse the clinical application of this retinal imaging-based technology.

Effect of ECG-gating Retinal Photographs on Retinal Vessel Caliber Measurements in Subjects with and without Type 2 Diabetes.

Purpose/Aim of this study: Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have been shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in healthy subjects. This cross-sectional study is the first study to investigate this issue in type 2 diabetes. The aim of this study was to determine whether ECG-gating retinal photographs reduce the variability in retinal arteriolar and venular caliber measurements in controls and type 2 diabetes.Materials and Methods: Fifteen controls and 15 patients with type 2 diabetes were arbitrarily recruited from Westmead Hospital, Sydney, Australia. A mydriatic fundoscope connected to our novel ECG synchronization unit captured 10 ECG-gated (at the QRS) and 10 ungated digital retinal photographs of the left eye in a randomized fashion, blinded to study participants. Two independent reviewers used an in-house semi-automated software to grade single cross-sectional vessel diameters across photographs, between 900 and 1800 microns from the optic disc edge. The coefficient of variation compared caliber variability between retinal arterioles and venules.Results: Our ECG synchronization unit reported the smallest time delay (33.1 ± 48.4 ms) in image capture known in the literature. All 30 participants demonstrated a higher reduction in retinal arteriolar (ungated: 1.02, 95%CI 0.88-1.17% vs ECG-gated: 0.39, 95%CI 0.29-0.49%, p < .0001) than venular (ungated 0.62, 95%CI 0.53-0.73% vs ECG-gated: 0.26, 95%CI 0.19-0.35%, p < .0001) coefficient of variation by ECG-gating photographs. Intra-observer repeatability and inter-observer reproducibility analysis reported high interclass correlation coefficients ranging from 0.80 to 0.86 and 0.80 to 0.93 respectively.Conclusion: ECG-gating photographs at the QRS are recommended for retinal vessel caliber analysis in controls and patients with type 2 diabetes as they refine measurements.

ASSOCIATION BETWEEN PLATELET INDICES AND RETINAL VEIN OCCLUSION: A Systematic Review and Meta-Analysis.

PURPOSE: Platelet count, mean platelet volume, platelet distribution width, and plateletcrit are standard indices of platelet activation that have been studied in retinal vein occlusion (RVO) and its subtypes: branch retinal vein occlusion and central retinal vein occlusion. This systematic review and meta-analysis aimed to assess the association between these platelet parameters and RVO. METHODS: We searched for studies investigating the association between these platelet indices and RVO in multiple online databases from inception to August 2020. Mean differences and the associated confidence intervals were obtained and calculated for each included study and pooled using random-effects inverse variance modeling. Meta-regression was used to explore interstudy and intrastudy heterogeneity. RESULTS: Thousand three hundred and twenty-five unique studies were screened, from which 24 studies encompassing 2,718 patients were included. Mean platelet volume and platelet distribution width were significantly elevated in RVO, with pooled mean differences of 0.45 fL (95% CI 0.24-0.66, P < 0.0001) and 1.43% (95% CI 0.57-2.29, P = 0.0011), respectively. Platelet count and plateletcrit were not significantly associated with RVO. Mean platelet volume was also independently elevated in branch retinal vein occlusion and central retinal vein occlusion. CONCLUSION: Mean platelet volume and platelet distribution width are significantly elevated in RVO. Further research is required to explore the independence and potential prognostic significance of these associations.

The AppNL-G-F mouse retina is a site for preclinical Alzheimer's disease diagnosis and research.

In this study, we report the results of a comprehensive phenotyping of the retina of the AppNL-G-F mouse. We demonstrate that soluble Aß accumulation is present in the retina of these mice early in life and progresses to Aß plaque formation by midlife. This rising Aß burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unaffected in the AppNL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aß, underscoring its potential as a biomarker for AD diagnosis and monitoring. These findings suggest that the AppNL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, offers unique opportunities for drug discovery and fundamental research into preclinical AD.

Diffuse Phlebitis in Patients with Syphilitic Outer Retinopathy.

Purpose: To report two cases of syphilitic outer retinopathy that showed diffuse phlebitis on fluorescein angiography (FA).Methods: Retrospective chart review.Results: The two patients had presentation similar to acute zonal occult outer retinopathy (AZOOR), including hyperautofluorescence on fundus autofluorescence and ellipsoid zone disruption on optical coherence tomography. The main difference from AZOOR was the finding of diffuse phlebitis on FA. Both patients recovered well after antibiotic and steroid treatment.Conclusion: FA is especially important for differentiating syphilitic outer retinopathy from AZOOR. Timely diagnosis and treatment with penicillin and cautious use of steroid usually lead to favorable prognosis.

The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model.

PURPOSE: Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. METHODS: In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. RESULTS: With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (ß = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (ß = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (ß = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure. CONCLUSION: We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.

Predictive values of initial semi-quantitative assessment of relative afferent pupillary defect for neovascularization in central retinal vein occlusion.

PURPOSE: To measure the predictive values of relative afferent pupillary defect (RAPD) assessed semi-quantitatively, and visual acuity (VA) at onset of central retinal vein occlusion (CRVO), for neovascularization. METHODS: Retrospective analysis of the TROXHEMO trial that included patients with CRVO within 30 days after the onset. Inclusion criteria were as follows: semi-quantitative RAPD assessment at diagnosis and/or at one month. RAPD was 'severe' if ≥ 0.9 log. Exclusion criteria were as follows: prophylactic panretinal photocoagulation (PRP) before neovascularization. RESULTS: Among the 119 patients enrolled in the main centre, 101 were analysed. 26 had a neovascular complication during the twelve months of follow-up: rubeosis (19), glaucoma (7) and posterior neovascularization (15). The mean time to onset of a neovascular complication was 4.7 months (1 to 12, median 3 months). All the patients who had a neovascular complication had RAPD at first examination or at one month (negative predictive value (NPV) = 100%) but the positive predictive value (PPV) was low (31%, 95% CI [21%; 42%]). The association 'severe RAPD or VA < 35 letters (ETDRS) at inclusion or at one month' was the best compromise between PPV (53%, [39%; 68%]) and NPV (96%, [92%; 100%]). CONCLUSION: To predict neovascularization, RAPD should be routinely evaluated with filters: the risk of neovascular complication is (a) almost nil if there is no RAPD, (b) very low if there is no severe RAPD and if VA is higher than 35 letters, and (c) higher than 50% if RAPD is ≥ 0.9 log or if VA is less than 35 letters.

Decreased Vascular Patterning in the Retinas of Astronaut Crew Members as New Measure of Ocular Damage in Spaceflight-Associated Neuro-ocular Syndrome.

Purpose: Ocular structural and functional changes, collectively termed spaceflight-associated neuro-ocular syndrome (SANS), have been described in astronauts undergoing long-duration missions in the microgravity environment of the International Space Station. We tested the hypothesis that retinal vascular remodeling, particularly by smaller vessels, mediates the chronic headward fluid shifts associated with SANS. Methods: As a retrospective study, arterial and venous patterns extracted from 30° infrared Heidelberg Spectralis retinal images of eight crew members acquired before and after six-month missions were analyzed with NASA's recently released VESsel GENeration Analysis (VESGEN) software. Output parameters included the fractal dimension and overall vessel length density that was further classified into large and small vascular branching generations. Vascular results were compared with SANS-associated clinical ocular measures. Results: Significant postflight decreases in Df, Lv, and in smaller but not larger vessels were quantified in 11 of 16 retinas for arteries and veins (P value for Df, Lv, and smaller vessels in all 16 retinas were ≤0.033). The greatest vascular decreases occurred in the only retina displaying clinical evidence of SANS by choroidal folds and optic disc edema. In the remaining 15 retinas, decreases in vascular density from Df and Lv ranged from minimal to high by a custom Subclinical Vascular Pathology Index. Conclusions: Together with VESGEN, the Subclinical Vascular Pathology Index may represent a new, useful SANS biomarker for advancing the understanding of SANS etiology and developing successful countermeasures for long duration space exploration in microgravity, although further research is required to better characterize retinal microvascular adaptations.