Retina

Patel NA, Yannuzzi NA, Lin J, Smiddy WE. A Cost-Effectiveness Analysis of Intravitreal Aflibercept for the Prevention of Progressive Diabetic Retinopathy. Ophthalmol Retina 2022;6(3):213-218.Abstract
PURPOSE: To calculate costs required to prevent center-involved diabetic macular edema (CI-DME) or proliferative diabetic retinopathy (PDR), and to improve the diabetic retinopathy severity score (DRSS) with intravitreal anti-VEGF injections, as reported for aflibercept in 2 randomized control trials. DESIGN: Cost-effectiveness analysis modeling based on published data. SUBJECTS: None. METHODS: Results from PANORAMA and the Diabetic Retinopathy Clinical Research Network Protocol W were analyzed. Parameters collected included DRSS, risk reduction of PDR, risk reduction of CI-DME, and the number of treatments required. Costs were modeled based on 2020 Medicare reimbursement data practice settings of hospital-based facility and nonfacility. MAIN OUTCOME MEASURES: Cost to prevent cases of PDR and CI-DME and to improve DRSS stage. RESULTS: Over 2 years in Protocol W, the cost required to prevent 1 case of PDR was $83 000 ($72 400) in the facility (nonfacility) setting; in PANORAMA, the corresponding 2-year costs were $89 400 ($75 000) for the 2-mg aflibercept every 16 weeks (2Q16) arm, and $91 200 ($89 900) for the 2-mg aflibercept every 8 weeks as needed (2Q8PRN) arm. To prevent 1 case of CI-DME with vision loss in Protocol W, the cost was $154 000 ($133 000). For all CI-DME, with and without vision loss, in PANORAMA, the costs to prevent a case were $70 900 ($59 500) for the 2Q16 arm and $90 000 ($88 800) for the 2Q8PRN arm. In Protocol W, the overall accumulated total for cost/DRSS unit change at the 2-year point for facility (nonfacility) setting was $2700 ($2400)/DRSS. In the first year alone, it was $2100 ($1800)/DRSS and in the second year, it was $6100 ($5300)/DRSS. CONCLUSIONS: There is a considerable cost associated with the prevention of PDR and CI-DME with intravitreal aflibercept injections. A price per unit of change in DRSS is a new parameter that might serve as a benchmark in future utility analyses that could be used to bring the perspective to cost-utility considerations.
Bannai D, Adhan I, Katz R, Kim LA, Keshavan M, Miller JB, Lizano P. Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography. Schizophr Bull 2022;48(1):80-89.Abstract
BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.
Li Y, Hall NE, Pershing S, Hyman L, Haller JA, Lee AY, Lee CS, Chiang M, Lum F, Miller JW, Lorch A, Elze T. Age, Gender, and Laterality of Retinal Vascular Occlusion: A Retrospective Study from the IRIS® Registry. Ophthalmol Retina 2022;6(2):161-171.Abstract
PURPOSE: Retinal vascular occlusion is a leading cause of profound irreversible visual loss, but the understanding of the disease is insufficient. We systematically investigated the age, gender, and laterality at the onset of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) in the Intelligent Research in Sight (IRIS®) Registry. DESIGN: Retrospective registry cohort. PARTICIPANTS: Patients with retinal vascular occlusion participating in the IRIS® Registry. METHODS: Patients who received a diagnosis of retinal vascular occlusion between 2013 and 2017 were included. Those with unspecified gender or laterality were excluded when conducting the relevant analyses. Patients were categorized into RAO, with subtypes transient retinal artery occlusion (TRAO), partial retinal artery occlusion (PRAO), branch retinal artery occlusion (BRAO), and central retinal artery occlusion (CRAO), and into RVO, with subtypes venous engorgement (VE), branch retinal vein occlusion (BRVO), and central retinal vein occlusion (CRVO). Age was evaluated as a categorical variable (5-year increments). We investigated the association of age, gender, and laterality with the onset frequency of retinal vascular occlusion subtypes. MAIN OUTCOME MEASURES: The frequency of onset of RAO and RVO subtypes by age, gender and laterality. RESULTS: A total of 1 251 476 patients with retinal vascular occlusion were included, 23.8% of whom had RAO, whereas 76.2% had RVO. Of these, 1 248 656 and 798 089 patients were selected for analyses relevant to gender and laterality, respectively. The onset frequency of all subtypes increased with age. PRAO, BRAO, CRAO, and CRVO presented more frequently in men (53.5%, 51.3%, 52.6%, and 50.4%, respectively), whereas TRAO, VE, and BRVO presented more frequently in women (54.9%, 56.0%, and 54.5% respectively). All RAO subtypes and BRVO showed a right-eye onset preference (TRAO, 51.7%; PRAO, 54.4%; BRAO, 53.5%; CRAO, 53.4%; and BRVO, 51.0%), whereas VE and CRVO exhibited a left-eye onset preference (53.3% and 50.9%, respectively). CONCLUSIONS: Although retinal vascular occlusion incidence increases with age regardless of subtypes, we found various subtype-specific disease-onset differences related to gender and, in particular, ocular laterality. These findings may improve understanding of the specific cause of retinal vascular occlusions of different subtypes and their relationships with structural and anatomic asymmetries of the vascular system.
Wai KM, Vingopoulos F, Garg I, Kasetty M, Silverman RF, Katz R, Laíns I, Miller JW, Husain D, Vavvas DG, Kim LA, Miller JB. Contrast sensitivity function in patients with macular disease and good visual acuity. Br J Ophthalmol 2022;106(6):839-844.Abstract
INTRODUCTION: Contrast sensitivity function (CSF) may better estimate a patient's visual function compared with visual acuity (VA). Our study evaluates the quick CSF (qCSF) method to measure visual function in eyes with macular disease and good letter acuity. METHODS: Patients with maculopathies (retinal vein occlusion, macula-off retinal detachment, dry age-related macular degeneration and wet age-related macular degeneration) and good letter acuity (VA ≥20/30) were included. The qCSF method uses an intelligent algorithm to measure CSF across multiple spatial frequencies. All maculopathy eyes combined and individual macular disease groups were compared with healthy control eyes. Main outcomes included area under the log CSF (AULCSF) and six CS thresholds ranging from 1 cycle per degree (cpd) to 18 cpd. RESULTS: 151 eyes with maculopathy and 93 control eyes with VA ≥20/30 were included. The presence of a maculopathy was associated with significant reduction in AULCSF (β: -0.174; p<0.001) and CS thresholds at all spatial frequencies except for 18 cpd (β: -0.094 to -0.200 log CS, all p<0.01) compared with controls. Reductions in CS thresholds were most notable at low and intermediate spatial frequencies (1.5 cpd, 3 cpd and 6 cpd). CONCLUSION: CSF measured with the qCSF active learning method was found to be significantly reduced in eyes affected by macular disease despite good VA compared with healthy control eyes. The qCSF method is a promising clinical tool to quantify subtle visual deficits that may otherwise go unrecognised by current testing methods.
Wang J, Cui Y, Vingopoulos F, Kasetty M, Silverman RF, Katz R, Kim L, Miller JB. Disorganisation of retinal inner layers is associated with reduced contrast sensitivity in retinal vein occlusion. Br J Ophthalmol 2022;106(2):241-245.Abstract
BACKGROUND/AIMS: To determine if disorganisation of retinal inner layers (DRIL) is associated with reduced contrast sensitivity (CS) in patients with retinal vein occlusion (RVO) with a history of macular oedema (ME). METHODS: Prospective, observational cohort study. Patients with a history of ME secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) from October 2017 to July 2019 at a single institution were included. Patients underwent complete ophthalmic examination, spectral domain optical coherence tomography (SD-OCT) and CS testing using the quick contrast sensitivity function (qCSF) method. Eyes with coexisting macular disease were excluded. SD-OCT images were analysed for presence and extent of DRIL, intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective foci, epiretinal membrane (ERM), external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption, central macular thickness (CMT) and central foveal thickness (CFT). Multivariable mixed-effect linear regressions were performed for the area under the log contrast sensitivity function (AULCSF) using Stata (StataCorp). P values <0.05 were considered significant. RESULTS: 58 visits from 31 patients were included (1.9±1.2 visits per patient). 29 (50%) were for CRVO. The average age was 63.9±10.5 years. On multivariable analysis, DRIL extent (p<0.001), CMT (p=0.007), CFT (p=0.024) and moderate cataract (p=0.001) were significantly associated with worse AULCSF. CONCLUSIONS: DRIL extent is associated with reduced CS in eyes with ME secondary to RVO. DRIL is an imaging feature that has important implications for visual function.
Georgakopoulos CD, Tsapardoni FN, Makri OE, Vavvas D. TWO-YEAR RESULTS OF INTRAVITREAL INJECTIONS OF AFLIBERCEPT IN COATS DISEASE: A CASE REPORT. Retin Cases Brief Rep 2022;16(4):473-478.Abstract
PURPOSE: To report long-term results of treatment with intravitreal injections of aflibercept in a newly diagnosed case of Coats disease. METHODS: An 18-year-old man presented to the retina clinic of our hospital complaining of blurred vision in the right eye for the past 3 months. His past medical and ocular history were unremarkable. The best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left eye. Fundoscopy in the right eye revealed extensive macular edema with a circinate ring of hard exudates in the posterior pole temporally to the macula. Optical coherence tomography demonstrated macular edema with subretinal fluid. Peripheral telangiectasias and light bulb aneurysms in the inferior temporal arcade as well as in the nasal far periphery were found in the right eye in fluorescein angiography, confirming the diagnosis of stage 2B Coats disease. The left eye was normal. RESULTS: The original therapeutic strategy proposed was antivascular endothelial growth factor injections in the right eye, followed by laser photocoagulation. However, the patient did not consent to laser treatment and was treated with aflibercept monotherapy with 8 monthly intravitreal injections of aflibercept, followed by 6 injections every 2 months for a total of 14 injections over a period of 2 years. The best-corrected visual acuity in the right eye improved to 20/25 while optical coherence tomography imaging revealed significant decrease in retinal thickness with resolution of macular edema, and fluorescein angiography demonstrated prominent regression of aneurysms and leakage. CONCLUSION: To the best of our knowledge, this is the first case treated with aflibercept monotherapy, suggesting the significant role of vascular endothelial growth factor in vascular permeability in Coats and supporting the rationale that antivascular endothelial growth factors are a valuable therapeutic option for Coats disease.
Wang JC, Lu Y, Sobrin L, Husain D. MULTIMODAL IMAGING IN ACUTE RETINAL NECROSIS PRESENTING WITH MACULAR INVOLVEMENT. Retin Cases Brief Rep 2022;16(3):347-350.Abstract
PURPOSE: To report an unusual case of early macular necrosis in acute retinal necrosis and its features on multimodal imaging. METHODS: Findings on fundus examination, laboratory workup, fluorescein angiography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 31-year-old healthy woman presented with 1 week of photophobia and central scotoma of the right eye. Initial examination revealed vitritis, hyperemia of the optic disc, and a yellow-white macular lesion without any peripheral findings. Peripheral involvement was first noted only 4 days later. The patient was diagnosed with acute retinal necrosis secondary to varicella zoster virus and was successfully treated with intravitreal and oral antiviral medications. Optical coherence tomography imaging of the macular lesion showed involvement of both the inner and outer retina. Optical coherence tomography angiography revealed a large flow void in the choriocapillaris, which has not been previously demonstrated. CONCLUSION: Multimodal imaging offers valuable information in the evaluation of patients with acute retinal necrosis.
Tomita Y, Qiu C, Bull E, Allen W, Kotoda Y, Talukdar S, Smith LEH, Fu Z. Müller glial responses compensate for degenerating photoreceptors in retinitis pigmentosa. Exp Mol Med 2021;Abstract
Photoreceptor degeneration caused by genetic defects leads to retinitis pigmentosa, a rare disease typically diagnosed in adolescents and young adults. In most cases, rod loss occurs first, followed by cone loss as well as altered function in cells connected to photoreceptors directly or indirectly. There remains a gap in our understanding of retinal cellular responses to photoreceptor abnormalities. Here, we utilized single-cell transcriptomics to investigate cellular responses in each major retinal cell type in retinitis pigmentosa model (P23H) mice vs. wild-type littermate mice. We found a significant decrease in the expression of genes associated with phototransduction, the inner/outer segment, photoreceptor cell cilium, and photoreceptor development in both rod and cone clusters, in line with the structural changes seen with immunohistochemistry. Accompanying this loss was a significant decrease in the expression of genes involved in metabolic pathways and energy production in both rods and cones. We found that in the Müller glia/astrocyte cluster, there was a significant increase in gene expression in pathways involving photoreceptor maintenance, while concomitant decreases were observed in rods and cones. Additionally, the expression of genes involved in mitochondrial localization and transport was increased in the Müller glia/astrocyte cluster. The Müller glial compensatory increase in the expression of genes downregulated in photoreceptors suggests that Müller glia adapt their transcriptome to support photoreceptors and could be thought of as general therapeutic targets to protect against retinal degeneration.
Sena DF, Kilian R, Liu S-H, Rizzo S, Virgili G. Pneumatic retinopexy versus scleral buckle for repairing simple rhegmatogenous retinal detachments. Cochrane Database Syst Rev 2021;11:CD008350.Abstract
BACKGROUND: A rhegmatogenous retinal detachment (RRD) is a separation of the neurosensory retina from the retinal pigment epithelium caused by a full-thickness break associated with vitreous traction. While pneumatic retinopexy (PR), scleral buckle (SB), and vitrectomy are all well-received surgical interventions for eyes with RRD, their relative effectiveness has remained controversial. OBJECTIVES: To assess the effectiveness and safety of PR versus SB or PR versus a combination treatment of SB and vitrectomy for people with RRD and to summarize any data on economic measures and quality of life. SEARCH METHODS: We searched CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 3); Ovid MEDLINE; Ovid Embase; and four other databases on 11 March 2021. We used no date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included all randomized or quasi-randomized controlled trials comparing the effectiveness of PR versus SB (with or without vitrectomy) for eyes with RRD. DATA COLLECTION AND ANALYSIS: After screening for eligibility, two review authors independently extracted study characteristics, methods, and outcomes. We followed systematic review standards as set by Cochrane. MAIN RESULTS: In this update, we identified and included one new randomized controlled trial. Together with two trials from the 2015 version of the review, we included three trials (276 eyes of 274 participants) comparing the effectiveness of PR versus SB. None compared PR versus a combined treatment of SB and vitrectomy.  Of the three trials, one was a small study (published in 1996) with 20 participants (20 eyes) enrolled in Ireland and followed for a mean of 16 months; the second (published in 1989) included 196 participants (198 eyes) in the US followed for at least six months, and the third (published in 2021) was conducted in Italy and enrolled 58 participants (58 eyes) with a follow-up of 12 months. Overall, poor reporting quality resulted in unclear or high risks of bias.  We found low-certainty evidence that PR may achieve retinal reattachment slightly less often than SB (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.81 to 1.02; I2 = 0%; 3 studies, 276 eyes). Eyes undergoing PR may also display a higher risk of recurrent retinal detachment (low-certainty evidence), but the RR estimates were very imprecise (RR 1.70, 95% CI 0.97 to 2.98; I2 = 0%; 3 studies, 276 eyes). All three studies described the final visual acuity (VA) after the two procedures. However, the results were reported using different metrics and could not be combined. One study (196 participants) reported the proportion of eyes with a final VA of 20/40 or greater and favored PR (RR 1.31, 95% CI 1.04 to 1.65; low-certainty evidence), whereas in the 2021 study, both groups showed an improvement in final VA and there was no evidence of a difference between the two (mean difference [MD] -0.03, 95% CI -0.25 to 0.19; low-certainty evidence). No study reported data on quality of life or economic measures. Postoperative safety outcomes generally favored PR versus SB (low/very low-certainty evidence); however, there was considerable uncertainty regarding the risk of any operative ocular adverse events (RR 0.55 CI 0.28 to 1.11; 276 eyes), glaucoma (RR 0.31, 95% CI 0.01 to 7.46; 198 eyes), macular pucker (RR 0.65, 95% CI 0.20 to 2.11; 256 eyes), proliferative vitreoretinopathy (RR 0.94, 95% CI 0.30 to 2.96; 276 eyes), and persistent diplopia (RR 0.24, 95% CI 0.03 to 2.09; 256 eyes). Eyes undergoing PR experienced fewer postoperative cataract developments (RR 0.40, 95% CI 0.21 to 0.75; 153 eyes), choroidal detachments (RR 0.17, 95% CI 0.05 to 0.57; 198 eyes), and myopic shift (RR 0.03, 95% CI 0.01 to 0.10; 256 eyes). AUTHORS' CONCLUSIONS: The current update confirms the findings of the previous review. PR may result in lower rates of reattachment and higher rates of recurrence than SB, but carries a lower burden of postoperative complications. The effects of these two procedures on other functional outcomes and quality of life remain uncertain. The available evidence remains insufficient and of low quality.
Cai LZ, Lin J, Starr MR, Obeid A, Ryan EH, Ryan C, Forbes NJ, Arias D, Ammar MJ, Patel LG, Capone A, Emerson GG, Joseph DP, Eliott D, Gupta OP, Regillo CD, Hsu J, Yonekawa Y, Yonekawa Y. PRO score: predictive scoring system for visual outcomes after rhegmatogenous retinal detachment repair. Br J Ophthalmol 2021;Abstract
BACKGROUND/AIMS: To compare risk factors for poor visual outcomes in patients undergoing primary rhegmatogenous retinal detachment (RRD) repair and to develop a scoring system. METHODS: Analysis of the Primary Retinal detachment Outcomes (PRO) study, a multicentre interventional cohort of consecutive primary RRD surgeries performed in 2015. The main outcome measure was a poor visual outcome (Snellen VA ≤20/200). RESULTS: A total of 1178 cases were included. The mean preoperative and postoperative logMARs were 1.1±1.1 (20/250) and 0.5±0.7 (20/63), respectively. Multivariable logistic regression identified preoperative risk factors predictive of poor visual outcomes (≤20/200), including proliferative vitreoretinopathy (PVR) (OR 1.26; 95% CI 1.13 to 1.40), history of antivascular endothelial growth factor (VEGF) injections (1.38; 1.11 to 1.71), >1-week vision loss (1.17; 1.08 to 1.27), ocular comorbidities (1.18; 1.00 to 1.38), poor presenting VA (1.06 per initial logMAR unit; 1.02 to 1.10) and age >70 (1.13; 1.04 to 1.23). The data were split into training (75%) and validation (25%) and a scoring system was developed and validated. The risk for poor visual outcomes was 8% with a total score of 0, 17% with 1, 29% with 2, 47% with 3, and 71% with 4 or higher. CONCLUSIONS: Independent risk factors were compared for poor visual outcomes after RRD surgery, which included PVR, anti-VEGF injections, vision loss >1 week, ocular comorbidities, presenting VA and older age. The PRO score was developed to provide a scoring system that may be useful in clinical practice.
Yemanyi F, Bora K, Blomfield AK, Wang Z, Chen J. Wnt Signaling in Inner Blood-Retinal Barrier Maintenance. Int J Mol Sci 2021;22(21)Abstract
The retina is a light-sensing ocular tissue that sends information to the brain to enable vision. The blood-retinal barrier (BRB) contributes to maintaining homeostasis in the retinal microenvironment by selectively regulating flux of molecules between systemic circulation and the retina. Maintaining such physiological balance is fundamental to visual function by facilitating the delivery of nutrients and oxygen and for protection from blood-borne toxins. The inner BRB (iBRB), composed mostly of inner retinal vasculature, controls substance exchange mainly via transportation processes between (paracellular) and through (transcellular) the retinal microvascular endothelium. Disruption of iBRB, characterized by retinal edema, is observed in many eye diseases and disturbs the physiological quiescence in the retina's extracellular space, resulting in vision loss. Consequently, understanding the mechanisms of iBRB formation, maintenance, and breakdown is pivotal to discovering potential targets to restore function to compromised physiological barriers. These unraveled targets can also inform potential drug delivery strategies across the BRB and the blood-brain barrier into retinas and brain tissues, respectively. This review summarizes mechanistic insights into the development and maintenance of iBRB in health and disease, with a specific focus on the Wnt signaling pathway and its regulatory role in both paracellular and transcellular transport across the retinal vascular endothelium.
Hellström A, Pivodic A, Gränse L, Lundgren P, Sjöbom U, Nilsson AK, Söderling H, Hård A-L, Smith LEH, Löfqvist CA. Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants. JAMA Netw Open 2021;4(10):e2128771.Abstract
Importance: Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. Objective: To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. Design, Setting, and Participants: This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. Main Outcomes and Measures: Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. Results: A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. Conclusions and Relevance: This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
Comin CH, Tsirukis DI, Sun Y, Xu X. Quantification of retinal blood leakage in fundus fluorescein angiography in a retinal angiogenesis model. Sci Rep 2021;11(1):19903.Abstract
Blood leakage from the vessels in the eye is the hallmark of many vascular eye diseases. One of the preclinical mouse models of retinal blood leakage, the very-low-density-lipoprotein receptor deficient mouse (Vldlr-/-), is used for drug screening and mechanistic studies. Vessel leakage is usually examined using Fundus fluorescein angiography (FFA). However, interpreting FFA images of the Vldlr-/- model is challenging as no automated and objective techniques exist for this model. A pipeline has been developed for quantifying leakage intensity and area including three tasks: (i) blood leakage identification, (ii) blood vessel segmentation, and (iii) image registration. Morphological operations followed by log-Gabor quadrature filters were used to identify leakage regions. In addition, a novel optic disk detection algorithm based on graph analysis was developed for registering the images at different timepoints. Blood leakage intensity and area measured by the methodology were compared to ground truth quantifications produced by two annotators. The relative difference between the quantifications from the method and those obtained from ground truth images was around 10% ± 6% for leakage intensity and 17% ± 8% for leakage region. The Pearson correlation coefficient between the method results and the ground truth was around 0.98 for leakage intensity and 0.94 for leakage region. Therefore, we presented a computational method for quantifying retinal vascular leakage and vessels using FFA in a preclinical angiogenesis model, the Vldlr-/- model.
Maidana DE, Gonzalez-Buendia L, Miller JW, Vavvas DG. Local photoreceptor cell death differences in the murine model of retinal detachment. Sci Rep 2021;11(1):18798.Abstract
To investigate local cell death differences in the attached and detached retina at different regions in a murine experimental retinal detachment model. Subretinal injection of sodium hyaluronate was performed in eight-week-old C57BL/6J mice. Retinal regions of interest were defined in relation to their distance from the peak of the retinal detachment, as follows: (1) attached central; (2) attached paracentral; (3) detached apex; and (4) detached base. At day 0, the outer nuclear layer cell count for the attached central, attached paracentral, detached apex, and detached base was 1247.60 ± 64.62, 1157.80 ± 163.33, 1264.00 ± 150.7, and 1013.80 ± 67.16 cells, respectively. There were significant differences between the detached base vs. attached central, and between detached base vs. detached apex at day 0. The detached apex region displayed a significant and progressive cell count reduction from day 0 to 14. In contrast, the detached base region did not show progressive retinal degeneration in this model. Moreover, only the detached apex region had a significant and progressive cell death rate compared to baseline. Immediate confounding changes with dramatic differences in cell death rates are present across regions of the detached retina. We speculate that mechanical and regional differences in the bullous detached retina can modify the rate of cell death in this model.
Musayeva A, Unkrig JC, Zhutdieva MB, Manicam C, Ruan Y, Laspas P, Chronopoulos P, Göbel ML, Pfeiffer N, Brochhausen C, Daiber A, Oelze M, Li H, Xia N, Gericke A. Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina. Cells 2021;10(9)Abstract
Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in the ganglion cell layer (GCL) of the retina and axons in the optic nerve. Retinal arteriole responses were measured in isolated retinas by video microscopy. The levels of reactive oxygen species (ROS) were assessed in retinal cryosections and redox gene expression was determined in isolated retinas by quantitative PCR. I/R markedly reduced cell number in the GCL and axon number in the optic nerve of the vehicle-treated mice. In contrast, only a negligible reduction in cell and axon number was observed following I/R in the betulinic acid-treated mice. Endothelial function was markedly reduced and ROS levels were increased in retinal arterioles of vehicle-exposed eyes following I/R, whereas betulinic acid partially prevented vascular endothelial dysfunction and ROS formation. Moreover, betulinic acid boosted mRNA expression for the antioxidant enzymes SOD3 and HO-1 following I/R. Our data provide evidence that betulinic acid protects from I/R injury in the mouse retina. Improvement of vascular endothelial function and the reduction in ROS levels appear to contribute to the neuroprotective effect.

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