ULTRASOUND BIOMICROSCOPY AND ECHOGENIC EXTERNAL MARKER ASSISTED INTRAOCULAR FOREIGN BODY REMOVAL.

PURPOSE: We report a novel method of intraoperative localization of a retained anterior intraocular foreign body (IOFB), using a combination of ultrasound biomicrosopy and an insulated needle. METHODS: A retrospective case report of a 56-year-old man who presented with a right eye IOFB. RESULTS: On presentation, vision was decreased in the right eye to count fingers with a small subconjunctival hemorrhage, but no other signs of a penetrating laceration. Orbital CT revealed an IOFB, and the initial vitrectomy failed to retrieve the IOFB. Then, during the subsequent vitrectomy, using an ultrasound compatible needle and an ultrasound biomicrosopy, we were able to precisely locate and remove the small anterior IOFB. CONCLUSION: Retained IOFBs can lead to severe irreversible vision loss if not promptly removed. Ancillary imaging modalities and localization techniques can help locate occult IOFBs in difficult cases.

Unexplained Vision Loss Associated With Intraocular Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment Repair.

Purpose: To evaluate the visual outcomes with unexplained vision loss during or after silicone oil (SO) tamponade. Methods: This multicenter retrospective case series comprised patients with unexplained vision loss associated with SO tamponade or its removal. Eyes with other clear secondary identifiable causes of vision loss were excluded. Results: Twenty-nine eyes of 28 patients (64% male) were identified. The mean age was 50 ± 13 years (range, 13-78 years). The mean duration of SO tamponade was 148 ± 38 days. Eighteen eyes (62%) developed unexplained vision loss while under SO; 11 (38%) had vision loss after SO removal. The most common optical coherence tomography (OCT) finding was ganglion cell layer (GCL) thinning (55%). Eyes with vision loss after SO removal had a mean logMAR best-corrected visual acuity (BCVA) of 0.6 ± 0.7 (Snellen 20/85) before SO tamponade and 1.2 ± 0.4 (20/340) before SO removal. By the last follow-up after SO removal, the BCVA had improved to 1.1 ± 0.4 (20/235). In eyes with vision loss after SO removal, the BCVA before SO removal was 0.7 ± 0.7 (20/104), which deteriorated to 1.4 ± 0.4 (20/458) 1 month after SO removal. By the last follow-up, the BCVA had improved to 1.0 ± 0.5 (20/219). Conclusions: Unexplained vision loss can occur during SO tamponade or after SO removal. Vision loss was associated with 1000-centistoke and 5000-centistoke oil and occurred in macula-off and macula-on retinal detachments. The duration of tamponade was 3 months or longer in the majority of eyes. Most eyes had GCL thinning on OCT. Gradual visual recovery can occur yet is often incomplete.

Vascular imaging findings in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a vascular disease among preterm infants involving incomplete or abnormal retinal vascularization and is a leading cause of preventable blindness globally. Measurements of ocular blood flow originating from a variety of imaging modalities, including colour Doppler imaging (CDI), fluorescein angiography (FA) and ocular coherence tomography angiography (OCTA), have been associated with changes in ROP patients. Herein, we discuss and summarize the relevant current literature on vascular imaging and ROP reviewed through December 2022. Differences in vascular imaging parameters between ROP patients and healthy controls are reviewed and summarized. The available data identify significantly increased peak systolic velocity (PSV) in the central retinal artery and ophthalmic artery as measured by CDI, increased vascular tortuosity as measured by FA, smaller foveal avascular zone (FAZ) as measured by FA and OCTA, and increased foveal vessel density (VD) and reduced parafoveal VD as measured by OCTA in ROP patients compared with controls. None of the above findings appear to reliably correlate with visual acuity. The studies currently available, however, are inconclusive and lack robust longitudinal data. Vascular imaging demonstrates the potential to aid in the diagnosis, management and monitoring of ROP, alongside retinal examination via indirect ophthalmoscopy and fundus photography.

Perinatal events and development of juvenile idiopathic arthritis-associated uveitis.

Uveitis is one of the most common manifestations of juvenile idiopathic arthritis (JIA). Currently, JIA is associated with decreased gut microbiota diversity. Studies confirm that perinatal events can cause aberrant microbial colonization. The objective of this study is to determine if JIA is associated with perinatal events with a secondary focus on these variables to the development of JIA-uveitis. 369 patients with strabismus (n = 200) or JIA (n = 196) were included in the study. Completed surveys (JIA 37; strabismus 18) collected data about birth route, pregnancy and labor complications, JIA medications, and the presence of eye disorders. Analysis indicates that there is no relationship between JIA development and the perinatal events investigated. Similarly, no significance was found between JIA-uveitis and birth route or labor complications. Pregnancy complications, namely gestational diabetes (GD), were statistically higher in the JIA group with uveitis compared to JIA without uveitis. The data from this survey study showed that JIA-uveitis was highly associated with pregnancy complications, particularly with GD. However, no statistically significant association was found between JIA and route of delivery, labor complications, or pregnancy complications. Further studies are needed to understand the ways that GD interrelates with the development of uveitis in JIA patients.

miR-92a and integrin expression in fibrovascular membranes in proliferative diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of vision impairment. The proliferative form of DR (PDR) involves fibrovascular membrane (FVM) formation at the vitreoretinal interface. MicroRNAs (miRNAs) are a class of non-coding RNA molecules that play an important role in gene regulation; a single miRNA could regulate multiple genes. We previously reported that miR-92a, a suppressor of integrins α5 and αv, was downregulated in DR. Considering the integrin's role in FVM pathology and the potential involvement of miR-92a in DR, we asked a question whether miR-92a could play a critical role in FVM pathology. We collected the FVM and epiretinal membranes of individuals with PDR and macular pucker (control) undergoing pars plana vitrectomy. The frozen sections of membranes were stained for α5 and αvß3 integrins. The miR-92a levels were assessed using real-time quantitative PCR. The FVMs of individuals with PDR stained brighter for integrin subunits α5 and αvß3 compared to the epiretinal membranes of subjects with macular pucker. miR-92a levels were decreased in FVM subjects. In conclusion, our studies demonstrate that miR-92a decrease is associated with an increase in integrins α5 and αvß3, thus contributing to the inflammatory milieu in PDR.

Cataract Formation Following Pars Plana Vitrectomy in the Pediatric Population.

PURPOSE: To analyze post-vitrectomy cataract formation in the pediatric population to elucidate the number of phakic children requiring cataract surgery following vitreous surgery and the perioperative factors affecting cataract development in these patients. METHODS: Eyes of pediatric patients that underwent phakic pars plana vitrectomy (PPV) with no prior cataract in a 10-year period were included. Analyses evaluated relationships between patient age and time to cataract surgery, as well as contributing factors for cataract formation. Final visual outcomes were also examined. Outcomes were collected for patient age at first vitrectomy, indication for vitrectomy, use of tamponade agents, history of ocular trauma, cataract status, and time to cataract surgery from first vitrectomy. RESULTS: Of 44 eyes analyzed, 27 (61%) were noted to have some degree of cataract formation. Of these, 15 (56%; 34% of total eyes) underwent cataract surgery. Use of octafluoropropane (P = .04) or silicone oil (P = .03) positively correlated with the need for cataract surgery in the total study group. Patients requiring cataract surgery had worse endpoint visual acuities than those who did not undergo surgery (P = .02), although this difference becomes less significant in follow-up over 2 years (P = .30). Patients who had cataracts but did not need cataract surgery showed an improvement in visual acuity (P = .04), but this was not demonstrated in patients who did need cataract surgery (P = .90). CONCLUSIONS: Pediatric eye care providers should be aware of the significant risk of cataract formation following a phakic PPV. [J Pediatr Ophthalmol Strabismus. 2023;60(6):421-426.].

Sub-tenon's vancomycin injection for subretinal abscess secondary to methicillin-resistant Staphylococcus aureus endogenous endophthalmitis: a case report and literature review.

PURPOSE: To report the use of a sub-tenon's vancomycin injection for treatment of subretinal abscess secondary to methicillin-resistant Staphylococcus aureus (MRSA) endogenous endophthalmitis (EE). METHODS: A 17-year-old male developed EE with subretinal abscess in his right eye secondary to MRSA bacteremia from axillary necrotizing fasciitis. Despite prompt treatment with intravenous vancomycin and an intravitreal vancomycin injection, the patient displayed minimal improvement. The patient was subsequently treated with a sub-tenon's vancomycin injection. The injection technique is described in detail, as well as a review of the treatment options available for bacterial subretinal abscesses. RESULTS: On presentation, exam revealed minimal vitritis and a large yellow subretinal abscess superotemporally extending close to macula with subretinal fluid inferotemporally involving macula. Four days post-intravitreal vancomycin injection, the abscess remained stable and the patient developed an exudative detachment temporally. Vancomycin was injected superotemporally in the sub-tenon's space with no complications during the procedure or during his post-operative recovery. At seven days post-injection, the subretinal abscess and exudative retinal detachment resolved completely with necrosis at the area of previous abscess. CONCLUSION: We present the first successful case of sub-tenon's vancomycin injection for the treatment of bacterial subretinal abscess. Our case demonstrates that sub-tenon's injection of antibiotics is a safe and effective non-surgical management option for bacterial subretinal abscesses.

The effect of axial length to basement-membrane opening to fovea distance on optical coherence tomography.

BACKGROUND: Optical Coherence Tomography (OCT) lateral scaling is influenced by axial length (AL). There is a need to incorporate a method to correct this measurement bias for accurate lateral OCT measurement. PURPOSE: To identify the correlation of optic-nerve-to-fovea distance measurement to AL by OCT) as an internal factor for lateral scaling. METHODS: Using Heidelberg Spectralis OCT, distance from the basement membrane opening at the optic disc margin to the centre of the fovea (BMO-fovea distance) was measured in 135 eyes (77 subjects, ages 25-85). These measurements were correlated with AL measurements from Zeiss IOLMaster 700 using linear regression before and after correction for ocular magnification. Statistical analysis including Shapiro-Wilk test for normality, Pearson correlation, and multivariate analysis of the association between disc-fovea distance and AL was performed using Wizard statistical software for mac. RESULTS: After lateral scaling, the mean distance between the fovea and BMO was 3.60 ± 0.25 mm (median: 3.59; range 3.07-4.23 mm). There was a significant positive correlation between AL and Bennett's formula-corrected BMO-fovea distance (p <0.001, r = 0.354). CONCLUSIONS: While there is significant variability in BMO-fovea distances, it is positively correlated with AL. A standard method is needed to improve the lateral scaling measurements in order to unify the results for enface OCT imaging.

Combining transfer learning with retinal lesion features for accurate detection of diabetic retinopathy.

Diabetic retinopathy (DR) is a late microvascular complication of Diabetes Mellitus (DM) that could lead to permanent blindness in patients, without early detection. Although adequate management of DM via regular eye examination can preserve vision in in 98% of the DR cases, DR screening and diagnoses based on clinical lesion features devised by expert clinicians; are costly, time-consuming and not sufficiently accurate. This raises the requirements for Artificial Intelligent (AI) systems which can accurately detect DR automatically and thus preventing DR before affecting vision. Hence, such systems can help clinician experts in certain cases and aid ophthalmologists in rapid diagnoses. To address such requirements, several approaches have been proposed in the literature that use Machine Learning (ML) and Deep Learning (DL) techniques to develop such systems. However, these approaches ignore the highly valuable clinical lesion features that could contribute significantly to the accurate detection of DR. Therefore, in this study we introduce a framework called DR-detector that employs the Extreme Gradient Boosting (XGBoost) ML model trained via the combination of the features extracted by the pretrained convolutional neural networks commonly known as transfer learning (TL) models and the clinical retinal lesion features for accurate detection of DR. The retinal lesion features are extracted via image segmentation technique using the UNET DL model and captures exudates (EXs), microaneurysms (MAs), and hemorrhages (HEMs) that are relevant lesions for DR detection. The feature combination approach implemented in DR-detector has been applied to two common TL models in the literature namely VGG-16 and ResNet-50. We trained the DR-detector model using a training dataset comprising of 1,840 color fundus images collected from e-ophtha, retinal lesions and APTOS 2019 Kaggle datasets of which 920 images are healthy. To validate the DR-detector model, we test the model on external dataset that consists of 81 healthy images collected from High-Resolution Fundus (HRF) dataset and MESSIDOR-2 datasets and 81 images with DR signs collected from Indian Diabetic Retinopathy Image Dataset (IDRID) dataset annotated for DR by expert. The experimental results show that the DR-detector model achieves a testing accuracy of 100% in detecting DR after training it with the combination of ResNet-50 and lesion features and 99.38% accuracy after training it with the combination of VGG-16 and lesion features. More importantly, the results also show a higher contribution of specific lesion features toward the performance of the DR-detector model. For instance, using only the hemorrhages feature to train the model, our model achieves an accuracy of 99.38 in detecting DR, which is higher than the accuracy when training the model with the combination of all lesion features (89%) and equal to the accuracy when training the model with the combination of all lesions and VGG-16 features together. This highlights the possibility of using only the clinical features, such as lesions that are clinically interpretable, to build the next generation of robust artificial intelligence (AI) systems with great clinical interpretability for DR detection. The code of the DR-detector framework is available on GitHub at https://github.com/Janga-Lab/DR-detector and can be readily employed for detecting DR from retinal image datasets.

Using optical coherence tomography angiography as a biomarker of retinopathy severity and treatment for diabetic retinopathy.

Purpose: The goal was to evaluate optical coherence tomography angiography (OCT-A) as a biomarker to correlate retinal vessel density (VD) with diabetic retinopathy (DR) severity and visual acuity, as well as track antivascular endothelial growth factor (VEGF) treatment efficacy. Methods: This retrospective cohort study analyzed the automatically quantified VDs of the superficial vascular complex (SVC) and deep vascular complex (DVC), including the whole, foveal, and parafoveal VDs, on quality OCT-A scans in patients diagnosed with DR. A multivariate linear regression and analysis of variance (ANOVA) analysis compared VDs to DR severity, visual acuity, and demographic factors. A linear mixed analysis determined the effects of VD by whether anti-VEGF therapy was given to patients with OCT-A scans at multiple time points. Results: There was a positive correlation of the VDs in both the SVC whole and parafoveal VD and DVC parafoveal VD with decreased DR severity and increased visual acuity (p≤0.001). The DVC whole VD was also positively correlated with increased visual acuity (p<0.001). There was no difference in the VDs associated with anti-VEGF treatment over time. Conclusions: OCT-A VD shows promise for diagnosing and monitoring DR using DR severity and visual acuity. Anti-VEGF treatment had no significant effect (p=0.063) on vascular density in diabetic retinopathy.

Progress in the pharmacotherapy of uveitis: the art of personalized care.

INTRODUCTION: Uveitis is a heterogeneous group of inflammatory intraocular disorders that can lead to blindness, but prompt diagnosis and management can improve visual outcomes and reduce treatment burden. AREAS COVERED: In this review, the authors provide an overview of commonly used treatments for the management of noninfectious uveitis. EXPERT OPINION: Initially, the treatment of noninfectious uveitis was limited to corticosteroids, which have a broad range of adverse ocular and systemic effects. Now new delivery and therapeutic options, such as biological response modulators, represent novel yet exciting additions to this armory and have the potential to alter the course of treatment as well as prognostic outcomes for uveitis patients. Further research is needed to evaluate the efficacy of this novel class of immunomodulators in uveitis therapy.

Clinical implications of retinal oximetry in retinal vein occlusion: a review.

PURPOSE: To review retinal vein occlusion (RVO) and its relationship with retinal oxygen saturation via automated retinal oximetry in eyes with RVO. METHODS: A literature review was performed in PubMed and Medline until October 2021 utilizing specific keywords and cross-matched reference lists. RESULTS: This review found RVO to be associated with risk factors including age, hypertension, cardiovascular and metabolic conditions, male gender, and glaucoma. These may be attributed to a breakdown of regulatory processes in the retina. Retinal venous oxygen saturation (SvO2 ) and arteriovenous difference in eyes with central RVO have been found to be reduced and elevated, respectively. The literature indicates variable and contradictory findings in regard to branch RVO and retinal oxygenation. Additionally, ischaemic eyes have been found to have elevated retinal arterial oxygen saturation; however, the literature reports variable results regarding SvO2 levels. Medications have been suggested to increase SvO2 in RVO eyes, which may represent an important mechanism for disease management. Ranibizumab is currently the most studied drug for retinal oxygenation in RVO and has been suggested to increase SvO2 in RVO eyes. In comparison, dexamethasone was found to decrease SvO2 . CONCLUSION: The current literature on retinal oxygenation in ischaemic subtypes of RVO and in drug therapies is minimal, and further work is required to expand upon our understanding of how ischaemia and drugs influence retinal oxygenation and clinical outcomes.

Modeling of external self-excitation and force generation on magnetic nanoparticles inside vitreous cavity.

The purpose of this manuscript was to design a better method for recovery from rhegmatogenous retinal detachment (RRD) surgery. We attempted to achieve this by designing a helmet that can manipulate intraocular magnetic nanoparticles (MNPs) and create a magnetic tamponade, eliminating the need for postoperative head positioning. A simulated analysis was developed to predict the pattern of magnetic force applied to the magnetic nanoparticles by external magnetic field. No participants were involved in this study. Instead, magnetic flux and force data for three different helmet designs were collected using virtual simulation tools. A prototype helmet was then constructed and magnetic flux and force data were recorded and compared to virtual data. For both virtual and physical scenarios, magnitude and direction of the resulting forces were compared to determine which design created the controlled direction and strongest forces into the back of the eye. Of the three virtual designs, both designs containing a visor had greater force magnitude than magnet alone. Between both designs with visors, the visor with bends resulted in forces more directed at the back of the eye. The physical prototype helmet shared similar measurements to virtual simulation with minimal percent error (Average = 5.47%, Standard deviation = 0.03). Of the three designs, the visor with bends generated stronger forces directed at the back of the eye, which is most appropriate for creating a tamponade on the retina. We believe that this design has shown promising capability for manipulating intraocular MNPs for the purpose of creating a tamponade for RRD.

The utility and risks of therapeutic nanotechnology in the retina.

The clinical application of nanotechnology in medicine is promising for therapeutic, diagnostic, and surgical improvements in the near future. Nanotechnologies in nano-ophthalmology are in the early stages of application in clinical contexts, including ocular drug and gene delivery systems addressing eye disorders, particularly retinopathies. Retinal diseases are challenging to treat as current interventions, such as intravitreal injections, are limited by their invasive nature. This review examines nanotechnological approaches to retinal diseases in a clinical context. Nanotechnology has the potential to transform pharmacological and surgical interventions by overcoming limitations posed by the protective anatomical and physiological barriers that limit access to the retina. Preclinical research in the application of nanoparticles in diagnostics indicates that nanoparticles can enhance existing diagnostic and screening tools to detect diseases earlier and more easily and improve disease progression monitoring precision.

MACULAR DETACHMENT ASSOCIATED WITH ANOMALOUS OPTIC NERVES AND DURAL ECTASIA IN 49, XXXXY SYNDROME.

PURPOSE: To present a case of a patient with XXXXY syndrome, anomalous optic nerves, and dural ectasia in conjunction with macular detachment. METHODS: Case report. RESULTS: A 3-year-old boy with XXXXY chromosomal abnormality presented with bilateral maculopathy. On evaluation, he was found to have anomalous optic disks with serous detachment of the left eye. Magnetic resonance imaging of the brain revealed bilateral optic nerve dural ectasia without evidence of elevated intracranial pressure. CONCLUSION: XXXXY syndrome, like the related condition of Klinefelter syndrome, can manifest with ocular abnormalities. In the present case, the dural ectasia may have facilitated access of cerebrospinal fluid through anomalous optic nerves, resulting in neurosensory detachment.

Reactivation of Retinopathy of Prematurity Three Years After Treatment With Bevacizumab.

Although intravitreal injection of anti-vascular endothelial growth factor agents (IVA) can induce rapid regression of retinopathy of prematurity (ROP), late reactivation of the ROP can occur in the form of tractional retinal detachment (TRD) from contracted recurrent extraretinal fibrovascular proliferation. The authors report a case of bilateral TRD for recurrent ROP in a 3-year-old, which is the latest-reported reactivation to date. The authors propose that persistent avascular retina in eyes that have undergone IVA for ROP receive laser ablation to prevent late recurrences. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:255-259.].

Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model.

Although corneal allotransplantation is performed in the immune-privileged cornea, many grafts are still rejected after transplantation. This study examined the role of chemokine receptor D6 expression in a corneal allograft rejection, investigated the modulation of D6 expression in cells, and determined the effect of D6 on graft survival. Interestingly, D6 was highly expressed in CD45 -: cells and the corneal epithelium of accepted corneal allografts. From the mouse corneal allograft model, TGF-ß was found to play a key role in D6 up-regulation, leading to reduced CCL2, CCL5, and CCL3. To modulate D6 chemokine binding, a D6MT was developed and showed effective chemokine trapping through SPR and FACS assays. By treating corneal allografts with D6MT, the allograft survival rate was improved, and (lymph) angiogenesis was reduced. Direct allosensitization and DC LN homing was drastically reduced in the mouse corneal allograft model. These findings suggest that TGF-ß is a positive regulator of D6 expression, and it is a potential therapeutic target to enhance the survival of corneal allografts.

Expression of the chemokine decoy receptor D6 mediates dendritic cell function and promotes corneal allograft rejection.

PURPOSE: To identify the role of chemokine receptor 6 (D6) expression by dendritic cells (DCs) and its role in corneal transplant immunity. METHODS: Flow cytometry analysis was used to assess the expression level of the D6 chemokine receptor in different leukocyte populations and DC maturation following lipopolysaccharides (LPS) stimulation of bone marrow-derived DCs isolated from wild-type (WT) or D6(-/-) mice (C57BL/6 background). Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were performed with bone marrow-derived DCs from WT or D6(-/-) mice to evaluate T-cell alloreactivity. Adoptive transfer experiments with T cells from WT or D6(-/-) hosts with BALB/c corneal allografts were performed. Graft opacity was assessed over an 8-week period, and graft survival was plotted using Kaplan-Meier survival curves. RESULTS: Expression of the D6 chemokine receptor was significantly higher in DCs compared to other leukocyte subpopulations, including neutrophils, lymphocytes, and monocytes/macrophages. LPS challenge of D6(-/-) bone marrow-derived DCs elicited significantly lower levels of major histocompatibility complex II and costimulatory molecules (CD40, CD80, and CD86) compared to WT bone marrow-derived DCs, indicating the role of the D6 chemokine receptor in DC maturation. Further, DCs isolated from D6(-/-) mice induced less T-cell proliferation (p≤0.001) and interferon-gamma production in T cells of draining lymph nodes compared to WT mice following corneal transplantation (p≤0.001). Moreover, adoptively transferred T cells from D6(-/-) corneal transplanted mice to WT mice led to impaired graft rejection, compared to the hosts that received T cells from the WT transplanted mice. CONCLUSIONS: We demonstrated D6 chemokine receptor expression by DCs and identified its critical function in multiple aspects of DC biology, including maturation and consequent elicitation of alloreactive T-cell responses that are responsible for corneal allograft rejection.