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Abstract This study investigates the efficacy of predicting age-related macular degeneration (AMD) activity through deep neural networks (DNN) using a cross-instrument training dataset composed of Optical coherence tomography-angiography (OCTA) images from two different manufacturers. A retrospective cross-sectional study analyzed 2D vascular en-face OCTA images from Heidelberg Spectralis (1478 samples: 1102 training, 276 validation, 100 testing) and Optovue Solix (1003 samples: 754 training, 189 validation, 60 testing). OCTA scans were labeled based on clinical diagnoses and adjacent B-scan OCT fluid information, categorizing activity into normal, dry AMD, active wet AMD, and wet AMD in remission. Experiments explored cross-instrument disease classification using separate and combined datasets for training the DNN. Testing involved 100 Heidelberg and 60 Optovue samples. Training on Heidelberg data alone yielded 73% accuracy on Heidelberg images and 60% on Optovue images. Training on Optovue data alone resulted in 34% accuracy on Heidelberg and 85% on Optovue images. Combined training data from both instruments achieved 78% accuracy on Heidelberg and 76% on Optovue test sets. Results indicate that cross-instrument classifier training demonstrates high classification prediction accuracy, making cross-instrument training viable for future clinical applications. This implies that vascular morphology in OCTA can predict disease progression.

Purpose: To report a case of iatrogenic trauma related choroidal neovascularization (CNV) Methods: A 66 year old female presented with complaints of distortion of vision in the right eye. A diagnosis of epiretinal membrane (ERM) foveoschisis was made and the patient was recommended surgery. During surgery an inadvertent touch of the retina occurred. Post operatively, an iatrogenic choroidal neovascular membrane was diagnosed. Results: Post-operative optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) revealed a CNV which was treated with intravitreal Bevacizumab. The visual acuity improved remarkably. The intraretinal and subretinal fluid resolved and the macula was almost completely dry at final visit. Conclusion: ERM surgery is one of the common procedures in vitreoretinal surgery. Iatrogenic CNV is a reported but rare complication following inadvertent trauma during surgery. We report a successful outcome of iatrogenic CNV treated with intravitreal injections of Bevacizumab.

PurposeTo determine the impact of severity of age-related macular degeneration (AMD) on subjective treatment response in patients treated for dry eye disease.MethodsA total of 203 eyes diagnosed with evaporative dry eye disease (DED) due to meibomian gland dysfunction were treated using the LipiFlow or MiBoFlo systems. From this cohort, 40 eyes with stable dry AMD (early, intermediate, or late stages) were included. Each participant completed the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) before treatment and at a 6-month follow-up. Changes in questionnaire scores were analyzed using one-way analysis of variance (ANOVA) to assess differences between AMD severity groups.ResultsImprovement in SPEED and OSDI scores, including vision related OSDI scores were observed across all AMD stages, with no significant differences between groups (pConclusionManaging DED improved quality of life (QOL) in patients with AMD, regardless of retinal disease severity. This highlights the importance of treating coexisting ocular surface conditions to enhance patient outcomes, even in the presence of significant maculopathy.

Abstract In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch’s Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.

Abstract This cross-sectional study aimed to investigate the hypothesis that permanent capillary damage may underlie the long-term COVID-19 sequela by quantifying the retinal vessel integrity. Participants were divided into three subgroups; Normal controls who had not been affected by COVID-19, mild COVID-19 cases who received out-patient care, and severe COVID-19 cases requiring intensive care unit (ICU) admission and respiratory support. Patients with systemic conditions that may affect the retinal vasculature before the diagnosis of COVID-19 infection were excluded. Participants underwent comprehensive ophthalmologic examination and retinal imaging obtained from Spectral-Domain Optical Coherence Tomography (SD-OCT), and vessel density using OCT Angiography. Sixty-one eyes from 31 individuals were studied. Retinal volume was significantly decreased in the outer 3 mm of the macula in the severe COVID-19 group (p = 0.02). Total retinal vessel density was significantly lower in the severe COVID-19 group compared to the normal and mild COVID-19 groups (p = 0.004 and 0.0057, respectively). The intermediate and deep capillary plexuses in the severe COVID-19 group were significantly lower compared to other groups (p

Abstract Comparing automated retinal layer segmentation using proprietary software (Heidelberg Spectralis HRA + OCT) and cross-platform Optical Coherence Tomography (OCT) segmentation software (Orion). Image segmentations of normal and diseased (iAMD, DME) eyes were performed using both softwares and then compared to the ‘gold standard’ of manual segmentation. A qualitative assessment and quantitative (layer volume) comparison of segmentations were performed. Segmented images from the two softwares were graded by two masked graders and in cases with difference, a senior retina specialist made a final independent decisive grading. Cross-platform software was significantly better than the proprietary software in the segmentation of NFL and INL layers in Normal eyes. It generated significantly better segmentation only for NFL in iAMD and for INL and OPL layers in DME eyes. In normal eyes, all retinal layer volumes calculated by the two softwares were moderate-strongly correlated except OUTLY. In iAMD eyes, GCIPL, INL, ONL, INLY, TRV layer volumes were moderate-strongly correlated between softwares. In eyes with DME, all layer volume values were moderate-strongly correlated between softwares. Cross-platform software can be used reliably in research settings to study the retinal layers as it compares well against manual segmentation and the commonly used proprietary software for both normal and diseased eyes.

Abstract Age-related macular degeneration and its complication, subretinal neovascularization, are common causes of progressive, irreversible impairment of central vision. Anti-vascular endothelial growth factor (anti-VEGF) therapy has improved the visual outcome and provided an evolution in the treatment of retinal disease. The current four anti-VEGF drugs – pegaptanib, ranibizumab, aflibercept, and bevacizumab – have been administered for many years. A new anti-VEGF agent, brolucizumab, was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for the treatment of wet age-related macular degeneration. Brolucizumab is a novel single-chain fragment variable antibody that inhibits all isoforms of VEGF-A and has been suggested to have more tissue penetration. Despite all the benefits, there are some reports of serious side effects that need to be understood in managing patients. Brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of intraocular inflammation, which has not been seen in other anti-VEGF medications. A PubMed and Scopus search was performed and all article types were included. In the present article, we have reviewed the reported side effects of brolucizumab.

We present a Keck/MOSFIRE rest-optical composite spectrum of 16 typical gravitationally lensed star-forming dwarf galaxies at 1.7 ≲ z ≲ 2.6 ( z _mean = 2.30), all chosen independent of emission-line strength. These galaxies have a median stellar mass of $\mathrm{log}{({M}_{* }/{M}_{\odot })}_{\mathrm{med}}={8.29}_{-0.43}^{+0.51}$ and a median star formation rate of ${{\rm{S}}{\rm{F}}{\rm{R}}}_{{\rm{H}}\alpha }^{{\rm{m}}{\rm{e}}{\rm{d}}}={2.25}_{-1.26}^{+2.15}\,{M}_{\odot }\,{{\rm{y}}{\rm{r}}}^{-1}$ . We measure the faint electron-temperature-sensitive [O iii ] λ 4363 emission line at 2.5 σ (4.1 σ ) significance when considering a bootstrapped (statistical-only) uncertainty spectrum. This yields a direct-method oxygen abundance of $12+\mathrm{log}{({\rm{O}}/{\rm{H}})}_{\mathrm{direct}}={7.88}_{-0.22}^{+0.25}$ ( ${0.15}_{-0.06}^{+0.12}\ {Z}_{\odot }$ ). We investigate the applicability at high z of locally calibrated oxygen-based strong-line metallicity relations, finding that the local reference calibrations of Bian et al. best reproduce (≲0.12 dex) our composite metallicity at fixed strong-line ratio. At fixed M _* , our composite is well represented by the z ∼ 2.3 direct-method stellar mass—gas-phase metallicity relation (MZR) of Sanders et al. When comparing to predicted MZRs from the IllustrisTNG and FIRE simulations, having recalculated our stellar masses with more realistic nonparametric star formation histories $(\mathrm{log}{({M}_{* }/{M}_{\odot })}_{\mathrm{med}}={8.92}_{-0.22}^{+0.31})$ , we find excellent agreement with the FIRE MZR. Our composite is consistent with no metallicity evolution, at fixed M _* and SFR, of the locally defined fundamental metallicity relation. We measure the doublet ratio [O ii ] λ 3729/[O ii ] λ 3726 = 1.56 ± 0.32 (1.51 ± 0.12) and a corresponding electron density of ${n}_{e}={1}_{-0}^{+215}\ {\mathrm{cm}}^{-3}$ ( ${n}_{e}={1}_{-0}^{+74}\ {\mathrm{cm}}^{-3}$ ) when considering the bootstrapped (statistical-only) error spectrum. This result suggests that lower-mass galaxies have lower densities than higher-mass galaxies at z ∼ 2.

Mesoporous silica has attracted significant attention in the drug delivery area; however, impurities can be a source of toxicity. The current study used commercial microparticles produced at large scale in a well-controlled environment. Micrometer sized mesoporous silica particles were acquired through a commercial vendor and pore structures were characterized by SEM. The three silica particle formulations had a diameter of 15 micrometers and three different pore sizes of 10 nm, 30 nm, and 100 nm. The fourth formulation had particle size of 20–40 micrometers with 50 nm pores. Before in vivo tests, an in vitro cytotoxicity test was conducted with silicic acid, derived from the sol-gel particles, on EA.hy926 cells. Low concentration (2.5 µg/mL) of silicic acid showed no cytotoxicity; however, high concentration (25 µg/mL) was cytotoxic. In vivo intravitreal injection demonstrated that 15 um silica particles with 10 nm pore were safe in both rabbit and guinea pig eyes and the particles lasted in the vitreous for longer than two months. Formulations of with larger pores demonstrated variable localized vitreous cloudiness around the sol-gel particle depot and mild inflammatory cells in the aqueous humor. The incidence of reaction trended higher with larger pores (10 nm: 0%, 30 nm: 29%, 50 nm: 71%, 100 nm: 100%, p

Proliferative vitreoretinopathy (PVR) is a significant threat for vision recovery from retinal detachment or ocular trauma. Currently, no approved pharmacological intervention to prevent PVR. Daunorubicin (DNR) and dexamethasone (DEX) were sequentially loaded into oxidized porous silicon (pSiO2) particles by covalent conjugation. The DNR + DEX-loaded particles, and control particles loaded with DNR only and DEX only were incubated with RPE-populated collagen for daily gel surface quantitation. Toxicity was monitored by ophthalmic examinations and histological evaluation 21 days after injection. At 3rd week following intravitreal injection, a localized retinal detachment (RD) was created by subretinal injection of Healon in all pretreated eyes in addition to 3 non-interventional control eyes. 10 µg of bromodeoxyuridine (BrdU) was injected into the vitreous 4 h before sacrifice on day 3 after RD induction. Retinal sections were stained for glial fibrillary green protein (GFAP) and BrdU to identify activated glial cells and retinal cell proliferation. The studies demonstrated that all three pSiO2 particle types were well tolerated in vivo. DNR alone and DNR + DEX combination formulations demonstrated equally strong suppression on gel contraction (least square mean area of the gel: control = 1.71 vs. 30DNR = 1.85 or 30/40Dual = 1.83, p

Background: Cardiovascular disease is the leading cause of mortality and disability worldwide. A noninvasive test that can detect underlying cardiovascular disease has the potential to identify patients at risk prior to the occurrence of adverse cardiovascular events. We sought to determine whether an easily observed imaging finding indicative of retinal ischemia, which we term ‘retinal ischemic perivascular lesions’ (RIPLs), could serve as a biomarker for cardiovascular disease. Methods: We reviewed optical coherence tomography (OCT) scans of individuals, with no underlying retinal pathology, obtained at UC San Diego Health from July 2014 to July 2019. We identified 84 patients with documented cardiovascular disease and 76 healthy controls. OCT scans were assessed for evidence of RIPLs. In addition, the 10-year atherosclerotic cardiovascular disease (ASCVD) risk calculator was used to risk-stratify the subjects into four different categories. Findings: Patients with documented cardiovascular disease had higher number of RIPLs compared to healthy controls (2.8 vs 0.8, p 37). The number of RIPLs in individuals with intermediate and high 10-year ASCVD risk scores was higher than in those with low ASCVD risk scores (1.7 vs 0.64, p = 0.02 and 2.9 vs 0.64, p 0.002, respectively). Interpretation: The presence of RIPLs, which are anatomical markers of prior retinal ischemic infarcts, is suggestive of coexisting cardiovascular disease. RIPLs detection, obtained from routine retinal scans, may thus provide an additional biomarker to identify patients at risk of developing adverse cardiovascular events. Funding: None.

Blinding retinal diseases become more epidemic as the population ages. These diseases, such as diabetic retinopathy and macular edema, are of chronic nature and require protracted drug presence at the disease site. A sustained intravitreal porous silicon delivery system with dexamethasone (pSiO2-COO-DEX) was evaluated in a new rabbit model of proliferative vitreoretinopathy (PVR) in a real treatment design. In contrast to the pretreatment design model, pSiO2-COO-DEX was intravitreally injected into the eyes with active inflammation. Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel induced a late-onset vitreoretinal inflammation that gradually developed into PVR. This method mimics the human disease better than PVR induced by either intravitreal cell injection or trauma. The pSiO2-COO-DEX intervened eyes had minimal PVR, while balanced saline solution or free dexamethasone intervened eyes had significantly more PVR formation. In addition, adding VEGF to the Matrigel for subretinal injection induced greater inflammation and retinal neovascularization in comparison to only Matrigel injected under the medullary ray. Clinical and pathological examinations, including fundus fluorescein angiography and optical coherence tomography, confirmed these changes. In the current study, neither subretinal injection of Matrigel or subretinal injection of VEGF and Matrigel induced choroidal neovascularization. However, the current PVR model demonstrates a chronic course with moderate severity, which may be useful for drug screening studies.

The number of blind and low vision persons in the US is projected to increase to 5.68 million by 2020. The eye diseases causing loss of vision are life-long, chronic, and often need protracted presence of therapeutics at the disease site to keep the disease in remission. In addition, multiple pathologies participate in the disease process and a single therapy seems insufficient to bring the disease under control and prevent vision loss. This study demonstrates the use of porous silicon (pSi) particles sequentially loaded with daunorubicin (DNR) and dexamethasone (DEX) to create a synergistic intravitreally injectable dual-drug delivery system. DEX targets chronic inflammation while DNR inhibits excessive cell proliferation as well as suppresses hypoxia-inducible factor 1 to reduce scarring. This pSi-based delivery system releases therapeutic concentrations of DNR for 100 days and DEX for over 165 days after a single dose. This intravitreal dual-drug delivery system is also well tolerated after injection into the rabbit eye model, attested by ocular biomicroscopy, ocular tonometry, electroretinography, and histology. This novel dual-drug delivery system opens an attractive modality for combination therapy to manage refractory chorioretinal diseases and further preclinical studies are warranted to evaluate its efficacy.

Proliferative vitreoretinopathy (PVR) is a blinding eye disease and there is no effective pharmacological measure to prevent PVR development. The difficulty comes from lack of potent antiproliferative agent and lack of sustained delivery to cover high-risk time window for PVR to develop. Lipid prodrug of PMEG, hexadecyloxypropyl 9-[(2-phosphonomethoxy)ethyl]guanine (HDP-PMEG), was prepared and was evaluated as a pharmacological adjuvant to surgical management of PVR. A dose-escalation study determined that the highest nontoxic dose for intravitreal use in pigmented rabbits was 3 µg per eye. The genotoxicity of HDP-PMEG was harnessed as a perioperative preventative measure against PVR in a rabbit eye model while the sustained intravitreal pharmacological effect was evaluated on a laser-induced fibrovascular model in rat eye. After intravitreal 3 µg, HDP-PMEG particles in the rabbit vitreous was visible for at least 6 weeks. A single 50-min intravitreal infusion of HDP-PMEG demonstrated significant inhibition of PVR formation when compared with the eyes infused with only BSS (BSS vs. HDP-PMEG: estimate = 1.14, OR = 3.1, p = .027). A single intravitreal 104 ng (equivalent to 3 µg for rabbit eye) of HDP-PMEG significantly inhibit laser-induced fibrovascular proliferation in rat eye by 55% (least square mean pixel, BSS = 4763569.5 vs. HDP-PMEG = 2148129.7, p