Deep Learning Assisted Imaging Methods to Facilitate Access to Ophthalmic Telepathology.

Purpose: To investigate the use of super-resolution imaging techniques to enable telepathology using low-cost commercial cameras. Design: Experimental study. Participants: A total of 139 ophthalmic pathology slides obtained from the Ophthalmic Pathology service at the University of California, Irvine. Methods: Denoising Diffusion Probabilistic Model (DDPM) was developed to predict super-resolution pathology slide images from low-resolution inputs. The model was pretrained using 150 000 images randomly sampled from the ImageNet dataset. Patch aggregation was used to generate large images with DDPM. The performance of DDPM was evaluated against that of generative adversarial networks (GANs) and Robust UNet, which were also trained on the same dataset. Main Outcome Measures: The performance of models trained to generate super-resolution output images from low-resolution input images can be evaluated by using the mean squared error (MSE) and Structural Similarity Index Measure (SSIM), as well as subjective grades provided by expert pathologist graders. Results: In total, our study included 110 training images, 9 validation images, and 20 testing images. The objective performance scores were averaged over patches generated from 20 test images. The DDPM-based approach with pretraining produced the best results, with an MSE score of 1.35e-5 and an SSIM score of 0.8987. A qualitative analysis of super-resolution images was conducted by expert 3 pathologists and 1 expert ophthalmic microscopist, and the average accuracy of identifying the correct ground truth images ranged from 25% to 70% (with an average accuracy of 46.5%) for widefield images and 25% to 60% (with an average accuracy of 38.25%) for individual patches. Conclusions: The DDPM-based approach with pretraining is assessed to be effective at super-resolution prediction for ophthalmic pathology slides both in terms of objective and subjective measures. The proposed methodology is expected to decrease the reliance on costly slide scanners for acquiring high-quality pathology slide images, while also streamlining clinical workflow and expanding the scope of ophthalmic telepathology. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Vitreoretinal surgery in the management of infectious and non-infectious uveitis - a narrative review.

PURPOSE: This study aims to conduct a narrative review about the current role of vitreoretinal surgery in the management of infectious and non-infectious uveitis. METHODS: This review was performed based on a search of the PubMed database or on relevant published papers according to our current knowledge. RESULTS: A total of 91 articles were identified in the literature review. With the advance of microincision vitrectomy surgery (MIVS), pars plana vitrectomy (PPV) has gained increasing popularity in the management of infectious and non-infectious uveitis. For diagnostic purposes, larger amounts of sample can be obtained by MIVS than traditional vitreous aspiration using needles. For treatment purposes, PPV removes vitreous opacities, decreases inflammatory cytokines and mediators of inflammation, and tackles related complications, including hypotony, epiretinal membrane, macular holes, and retinal detachment. Achieving optimum control of inflammation prior to surgery is important for surgical interventions for non-emergent therapeutic indications and complications of uveitis. Peri-operative inflammation management is essential for decreasing the risk of surgical intervention. An overall complication rate of 42-54% was reported with cataract to be the leading cause of complications. CONCLUSION: Most reports affirm the role of PPV in the management of infectious and non-infectious uveitis, although the quality of data remains limited by a lack of applying standardized reporting outcomes, limitations in study design, and a paucity of prospective data.

microRNA 146a ameliorates retinal damage in experimental autoimmune uveitis.

Introduction: Uveitis and related intraocular inflammations are a major cause of blindness due to retinal damage caused by degeneration and loss of the photoreceptor cells. In mouse experimental autoimmune uveitis (EAU) previously we have shown mitochondrial oxidative stress with marked upregulation of αA crystallin in the inner segments of the photoreceptors. Furthermore, αA crystallin treatment prevented photoreceptor mitochondrial oxidative stress by suppressing innate and adaptive immunity in EAU. Methods: Since these immune processes are modulated by microRNAs, in this study we investigated (a) modulation of microRNAs during development of EAU by αA crystallin administration and (b) microRNA therapeutic intervention. Results: Few microRNAs were significantly upregulated in EAU mice with intravenous injection of αA crystallin and among these, computational bioinformatic analysis revealed that the upregulated microRNA 146a targets the innate and adaptive immune responses. In EAU, intravenous as well as intravitreal administration of this microRNA prevented inflammatory cell infiltration in uvea and retina and preserved photoreceptor cells. Discussion: This protective function suggests that microRNA146a can be a novel therapeutic agent in preventing retinal damage in uveitis.

Two Cases of Cutibacterium acnes (C acnes) Endophthalmitis Manifesting With Unusual Epiretinal Deposits.

This article describes two cases of delayed-onset Cutibacterium acnes (C acnes) endophthalmitis 1 month after cataract surgery manifesting with unusual epiretinal deposits. Both patients were referred for persistent inflammation after cataract surgery. After failing to respond to a vitreous tap with injection of antibiotics, the patients underwent pars plana vitrectomy and in one of the cases partial posterior capsulectomy for a posterior capsular plaque. Intraoperatively, both cases were found to have unusual multifocal epiretinal deposits. The clinical presentations described here represent a highly unique manifestation of C acnes endophthalmitis distinct from the classic anterior segment findings. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:164-167.].

Progress in the diagnosis of ocular sarcoidosis.

Sarcoidosis is a multisystem granulomatous inflammation that affects multiple organ systems. The spectrum of extraocular and ocular involvement is wide and may precede systemic involvement. The diagnosis of ocular sarcoidosis relies on a combination of clinical findings, laboratory investigations, and radiographic findings. These include but are not limited to serum angiotensin-converting enzyme (ACE), lysozyme, plain-film radiographs of the chest, computed tomography (CT) scans of the chest, pulmonary function testing, bronchoalveolar lavage, and retinal imaging among others. In this review, we highlight current and evolving systemic investigations and approaches to ophthalmic imaging when considering the diagnosis of ocular sarcoidosis.

ENDOGENOUS ASPERGILLUS ENDOPHTHALMITIS IN AN IMMUNOCOMPETENT PATIENT WITH A REMOTE HISTORY OF PULMONARY TUBERCULOSIS.

PURPOSE: To report a case of Aspergillus fumigatus endogenous endophthalmitis in an immunocompetent patient initially diagnosed as acute retinal necrosis. METHODS: Case report. PATIENT: A 67-year-old woman with a remote history of treated pulmonary tuberculosis and no ocular history presented to an outside retina specialist with a sudden onset of floaters and blurred vision in one eye. Examination and fluorescein angiography at the time revealed findings suspicious for acute retinal necrosis, and the patient was started on oral valganciclovir and an intravitreal injection of ganciclovir. Despite treatment, the patient's vision and pain worsened. After evaluation at the University of Southern California Roski Eye Institute, she was diagnosed with a likely fungal endogenous endophthalmitis based on ultrasound findings and underwent emergent vitrectomy. A chest x-ray demonstrated partial collapse of the right upper lobe with hilar enlargement. RESULTS: Aspergillus fumigatus was cultured from vitreous, blood, and bronchoalveolar lavage samples, suggesting that the patient's infection had a pulmonary origin, most likely from the right upper lobe that had healed from previous tuberculosis infection. DISCUSSION: To the best of our knowledge, this is the first reported case of Aspergillus endogenous endophthalmitis in an immunocompetent patient secondary to pulmonary changes that occurred from previously treated tuberculosis.

Electroretinogram and Visual Field Correlation in Birdshot Chorioretinopathy.

PURPOSE: The aim of this study was to assess possible correlation between the visual field and electroretinogram (ERG) parameters in birdshot chorioretinopathy (BCR). DESIGN: Retrospective cross-sectional study. METHODS: This single-center study included 21 eyes of 11 patients with BCR with prior ERG and Goldmann kinetic perimetry. Generalized estimating equation was used for statistical analysis, and isopters V4e and I4e were modeled as separate outcomes with each parameter of ERG as the main independent variable. The main outcome measure was presence or absence of correlation between the Goldmann isopters and ERG parameters including the amplitudes and implicit times of dark adapted (DA) and light adapted (LA) a-waves and b-waves (DA 0.01, DA 3.0, DA 10.0, and LA 3.0) and LA 30 Hz. RESULTS: There was a strong positive correlation between the size of isopter V4e and all the scotopic and photopic standard ERG amplitudes [P < 0.0001 for all, except LA 3.0 a-wave (P = 0.0019) and LA 30 Hz (P = 0.0026)]. For the implicit times, only DA 3.0 a-wave (P = 0.007) and LA 30 Hz (P < 0.0001) showed significant negative correlations. There were no correlations between the size of isopter I4e and any ERG amplitudes; however, 3 implicit times showed some negative correlation: DA 3.0 a-wave (P < 0.0001), DA 10.0 b-wave (P = 0.0251), and LA 3.0 b-wave (P < 0.0001). CONCLUSIONS: In this study, the largest isopter of Glodmann visual field showed a strong positive correlation with all standard ERG amplitudes in BCR. This novel finding underscores the role of ERG as an objective visual function test in monitoring the disease activity.

Relationship of Epiretinal Membrane Formation and Macular Edema Development in a Large Cohort of Uveitic Eyes.

Purpose: To identify the temporal relationship and clinical characteristics of epiretinal membrane (ERM) and macular edema (ME) formation in uveitic eyes.Methods: A total of 269 subjects (444 uveitic eyes) met study inclusion criteria. Comprehensive ophthalmic examination, spectral domain-optical coherence tomography (SD-OCT), and clinical testing were carried out.Results: Of the 444 uveitic eyes, 229 eyes (51.6%) developed an ERM, whereas 87 eyes (19.1%) developed ME. The odds ratios (ORs) of systemic disease causing uveitis and resulting in ERM and ME were significantly higher in posterior uveitis (OR 6.56, 95% CI 2.98-14.46; p < .0001) and panuveitis (OR 10.09, 95% CI 4.05-25.15; p < .0001). Temporal analysis revealed that an ERM was noted concurrently or prior to ME development in 93.8% of eyes.Conclusions: ERM and ME are primarily observed in posterior uveitis and panuveitis associated with systemic diseases. The temporal relationship highlights the importance of characterization of ERM as it relates to the development of uveitic ME.

Recommendations for the management of ocular sarcoidosis from the International Workshop on Ocular Sarcoidosis.

AIMS: To establish expert recommendations for the management of ocular sarcoidosis (OS). METHODS: A question-based survey on the management of OS was circulated to international uveitis experts (members of the International Uveitis Study Group and the International Ocular Inflammation Society) electronically. Subsequently, a consensus workshop was conducted at the 7th International Workshop on Ocular Sarcoidosis (IWOS) in June 2019 in Sapporo, Japan as part of the Global Ocular Inflammation Workshops. Statements on the management of OS that were supported by a two-thirds majority of 10 international panel members of the workshop, after discussion and voting, were taken as consensus agreement. RESULTS: A total of 98 participants from 29 countries responded to the questionnaire survey. The subsequent consensus workshop established recommendations for the management of OS in five sections. The first section concerned evaluation and monitoring of inflammation. The second, third and fourth sections described ocular manifestations that were indications for treatment, and the management of anterior uveitis, intermediate uveitis and posterior uveitis. In the fifth section, the use of systemic corticosteroids and systemic immunosuppressive drugs were detailed. CONCLUSIONS: Recommendations for management of OS were formulated through an IWOS consensus workshop.

Pathogenesis of ocular tuberculosis: New observations and future directions.

Ocular tuberculosis (OTB) encompasses all forms of intra- and extra-ocular inflammation associated with Mycobacterium tuberculosis (Mtb) infection. However, the organism is rarely found in ocular fluid samples of diseased eyes, rendering the pathomechanisms of the disease unclear. This confounds clinical decision-making in diagnosis and treatment of OTB. Here, we critically review existing human and animal data related to ocular inflammation and TB pathogenesis to unravel likely pathomechanisms of OTB. Broadly there appear to be two fundamental mechanisms that may underlie the development of TB-associated ocular inflammation: a. inflammatory response to live/replicating Mtb in the eye, and b. immune mediated ocular inflammation induced by non-viable Mtb or its components in the eye. This distinction is significant as in direct Mtb-driven mechanisms, diagnosis and treatment would be aimed at detection of Mtb-infection and its elimination; while indirect mechanisms would primarily require anti-inflammatory therapy with adjunctive anti-TB therapy. Further, we discuss how that most clinical phenotypes of OTB likely represent a combination of both mechanisms, with one being predominant than the other.

Ocular erythema nodosum leprosum: An immunohistochemical study.

Episcleritis, scleritis, and anterior uveitis are common clinical manifestations of ocular leprosy. Erythema nodosum leprosum (ENL) is an acute, exaggerated systemic immunological reaction that complicates the course of this chronic indolent disease. We present an ocular immunohistochemical study of severe form of ENL involving even the ciliary body and choroid resulting in the perforation of the globe on the initiation of anti leprosy therapy. We used CD-3, CD-68, S-100, and CD-20 for immunohistochemistry. It revealed plenty of CD-3-positive T-cells and CD-68-positive macrophages and a few S-100 and CD-20-positive cells. The inflammatory exudates stained positive for IgG and IgM. The diagnosis was ocular ENL.

Multimodal imaging reveals pathological edges of disease activity in tuberculosis-associated multifocal serpiginoid chorioiditis.

Tuberculosis associated serpiginous-like choroidopathy can lead to significant vision loss. The anatomical cause for this visual decline can be elucidated using multimodal retinal imaging. Imaging modalities used in this case, most notably, optical coherence tomography angiography (OCTA), demonstrated specific atrophy of the choriocapillaris.

Prognostic factors for TB-associated uveitis in the Asia-Pacific Region: results of a modified Delphi survey.

BACKGROUND: Prognostic factors for TB-associated uveitis (TBU) remain mostly unknown, due to the challenges in interpretation of patient data. We present consensus list of prognostic factors for resolution of inflammation in TBU, by experts across the Asia-Pacific region. METHODS: We applied a modified Delphi technique to generate consensus on prognostic factors influencing the resolution of inflammation in TB-associated: anterior uveitis (AU), retinal vasculitis (RV), and multifocal serpiginoid choroiditis (MSC). The initial questionnaire was developed through a face-to-face meeting. Sixteen uveitis experts from eleven Asia-Pacific countries were included. A single investigator circulated the questionnaire electronically and received the responses. Participants scored each item on 4-point Likert scale, in three successive rounds. After each round, a number of items were reduced based on response, and summary of responses was provided to participants. At the end of Round 3, items were considered significant if they: (1) achieved a median ≥2, and interquartile range ≤1, and (2) ≥75% of the respondents agreed on whether the item was a positive or negative prognostic factor. RESULTS: Forty-two putative questionnaire items were considered. At the end of Rounds 3, 4, 9, and 8 items in AU, RV, and MSC, respectively, met significance criteria. These included duration of disease, previous corticosteroid/immunosuppressive therapy, co-existent HIV, disease-specific imaging features, multidrug resistant TB, and duration of anti-TB therapy. CONCLUSIONS: Consensus were achieved on multiple ocular and systemic factors that influence resolution of inflammation in TBU. These will form the groundwork for validation in prospective clinical trials.