Overview of Cytomegalovirus Ocular Diseases: Retinitis, Corneal Endotheliitis, and Iridocyclitis.

Cytomegalovirus (CMV) infection is a significant clinical concern in newborns, immunocompromised patients with acquired immunodeficiency syndrome (AIDS), and patients undergoing immunosuppressive therapy or chemotherapy. CMV infection affects many organs, such as the lungs, digestive organs, the central nerve system, and eyes. In addition, CMV infection sometimes occurs in immunocompetent individuals. CMV ocular diseases includes retinitis, corneal endotheliitis, and iridocyclitis. CMV retinitis often develops in infected newborns and immunocompromised patients. CMV corneal endotheliitis and iridocyclitis sometimes develop in immunocompetent individuals. Systemic infections and CMV ocular diseases often require systemic treatment in addition to topical treatment.

Unveiling Key Pathological Indicators for Disease Progression in Vogt Koyanagi Harada Disease and Sympathetic Ophthalmia Through Advanced Choroidal Volume Analysis.

PURPOSE: To evaluate the association between quantitative parameters derived from volume analysis of optical coherence tomography (OCT) data and disease worsening in Vogt-Koyanagi-Harada disease (VKHD) and sympathetic ophthalmia (SO). METHODS: This retrospective study, conducted at Osaka University Hospital, employed swept-source OCT scans from patients diagnosed with VKHD or SO between October 2012 and January 2021. The choroidal vessel structure was segmented and visualized in three dimensions, generating quantitative vessel volume maps. Region-specific choroidal vessel volume (CVV), choroidal volume (CV), and vessel index (VI) were scrutinized for their potential correlation with disease severity. RESULTS: Thirty-five eyes of 18 VKHD and 2 SO patient (8 females, 10 males) were evaluated. OCT-derived CVV maps revealed regional CV alterations in VKHD and SO patients. Two parameters, i.e. CV at 3- and 6-month follow-ups (p = 0.044, p = 0.040, respectively, with area under the ROC curve of 0.70) and CVV at 6 months (p = 0.046, area under the ROC curve of 0.71), were significantly higher in recurrent VKHD and SO compared to effectively treated cases. CONCLUSIONS: The volume analysis of OCT images facilitates a three-dimensional visualization of choroidal alterations, which may serve as a reflection of disease severity in VKHD and SO patients. Furthermore, noninvasive initial CVV or CV measurements may serve as potential biomarkers for predicting disease recurrence in VKHD and SO.

Intensity-Modulated Radiation Therapy for Bilateral Choroidal Metastases Involving Macula and Optic Disc.

This case report discusses the case of a 76-year-old woman with choroidal metastasis from breast cancer who was treated with intensity-modulated radiation therapy (IMRT). Choroidal metastasis is a common ocular tumor, and the occurrence of this condition has increased due to improved diagnostic tools and longer survival of metastatic patients. IMRT is an innovative radiation therapy technique that reduces complications and improves the curative effect by concentrating radiation on the tumor while minimizing exposure to surrounding tissues. In this case, the patient had a history of breast cancer and was undergoing chemotherapy when she presented with vision loss and blurred vision. Imaging tests confirmed choroidal metastasis, and IMRT was performed under the guidance of a radiation oncologist. After treatment, the choroidal lesion dramatically reduced in size, and the patient's vision improved. The text concludes that radiation therapy, including IMRT, is becoming more common as a treatment for ocular metastasis to improve vision and preserve the eye. When choosing radiation therapy, it is essential to consider the size of the tumor and the impact on surrounding tissues. IMRT is an effective treatment that enables precise and concentrated irradiation of the tumor tissue while minimizing exposure to normal tissues.

Comparative evaluation of 16S rRNA metagenomic sequencing in the diagnosis and understanding of bacterial endophthalmitis.

OBJECTIVE: To evaluate the usefulness of metagenomic analysis in the search for causative organisms of bacterial endophthalmitis. METHODS AND ANALYSIS: Twenty-one consecutive treatment-naïve patients (13 men and 8 women; mean age, 60.8±19.8 years) with suspected endophthalmitis were recruited. Vitrectomy was performed to diagnose and treat endophthalmitis. Bacterial culture and metagenomic analysis of the vitreous body were performed. Extracted DNA was analysed using 16S rRNA sequences, and libraries were sequenced on an Illumina MiSeq sequencer. To compare the bacterial composition in each case, α and ß diversities were determined. RESULTS: Patients were categorised into three groups: endophthalmitis cases with matching predominant organisms according to metagenomic analysis and bacterial culture, those with negative results for bacterial culture and those with negative results in both cases. In 7 of 15 culture-negative cases, results from metagenomic analysis could detect pathogens. The diversity of bacterial populations was significantly lower in the group with positive results for predominant bacteria according to culture and metagenomic analysis. All patients with uveitis were included in the group for which the causative pathogen could not be determined by culture or metagenomic analysis. The structures of bacterial populations significantly differed between the positive and negative groups by culture and metagenomic analysis. CONCLUSIONS: Metagenomic analysis could be useful for prompt detection of causative pathogens, for precise diagnosis of infection, and as a marker of inflammation processes such as uveitis.

Fungal dysbiosis and decreased tear mucin at the conjunctiva in patients with conjunctival mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: This study aimed to examine the differences in the fungal microbiome between patients with conjunctival mucosa-associated lymphoid tissue (MALT) and healthy controls using metagenomic analysis. METHODS AND ANALYSIS: This case-control study was conducted at Osaka University Hospital in Osaka, Japan, from April 2015 to March 2022. Twenty-five consecutive patients with conjunctival MALT lymphoma and 25 healthy volunteers were included. Metagenomic analysis using Internal Transcribed Spacer (ITS)1 deep sequencing and hierarchical clustering was performed to investigate differences in the fungal microbiome. To assess tear environmental change, we measured tear mucin concentrations using ELISA. RESULTS: Detailed analyses showed fungal dysbiosis and changes in ß-diversity within the conjunctiva of patients with conjunctival MALT lymphoma. Hierarchical clustering revealed that the participants could be divided into three clusters according to the Malassezia abundance: cluster I (Malassezia abundance above 70%), cluster II (Malassezia abundance 25%-70%) and cluster II (Malassezia abundance below 25%). Most patients were included in cluster I, whereas most of healthy controls were included in cluster III. The differences were significant. Tear mucin concentrations were significantly lower in patients with MALT compared with healthy controls. CONCLUSION: The metagenomic analysis using ITS1 deep sequencing was useful for identifying the differences in commensal fungi between patients with MALT lymphoma and healthy individuals. The increased prevalence of the Malassezia genus and the decreased levels of tear mucin can lead to an allergic response of the conjunctiva, resulting in the pathogenesis associated with conjunctival MALT lymphoma. Therefore, it may be beneficial to initiate treatment when a high abundance Malassezia is detected.

Recent advances and future prospects: Current status and challenges of the intraocular injection of drugs for vitreoretinal diseases.

Effective drug therapy for vitreoretinal disease is a major challenge in the field of ophthalmology; various protective systems, including anatomical and physiological barriers, complicate drug delivery to precise targets. However, as the eye is a closed cavity, it is an ideal target for local administration. Various types of drug delivery systems have been investigated that take advantage of this aspect of the eye, enhancing ocular permeability and optimizing local drug concentrations. Many drugs, mainly anti-VEGF drugs, have been evaluated in clinical trials and have provided clinical benefit to many patients. In the near future, innovative drug delivery systems will be developed to avoid frequent intravitreal administration of drugs and maintain effective drug concentrations for a long period of time. Here, we review the published literature on various drugs and administration routes and current clinical applications. Recent advances in drug delivery systems are discussed along with future prospects.

Long-term course with iris changes after trabeculectomy for uveitic glaucoma associated with iris mammillation: a case report.

BACKGROUND: Iris mammillation is a rare disease characterized by the distribution of multiple nodules on the iris surface. The course of uveitic glaucoma with iris mammillation has never been reported. CASE PRESENTATION: A 56-year-old woman, who presented with unilateral decreased vision, visited our hospital for treatment of uveitic glaucoma in the right eye. Multiple nodules were scattered over the iris surface in that eye. This case was diagnosed as iris mammillation on clinical findings. After excluding malignant tumors such as melanoma, trabeculectomy was performed. The resected iris had no pathologically malignant findings. The iris nodules evolved to a sand-like appearance, and the intraocular pressure remained stable without recurrent inflammation 7 years after trabeculectomy. CONCLUSIONS: In a case of unilateral uveitic glaucoma with iris mammillation, filtration surgery was performed after excluding the presence of a malignancy, and the long-term postoperative course has been stable.

Idiopathic Multicentric Castleman Disease Presenting With Hypertensive Choroidopathy: A Case Report.

Castleman disease (CD) is a lymphoproliferative disorder and rarely affects ocular tissue. This study aimed to report a case of hypertensive choroidopathy in a patient with Castleman's disease associated with malignant hypertension. A 39-year-old man visited his local physician with fever, systemic edema, and multiple lymphadenopathies. An inguinal lymph node biopsy indicated CD. One month after the biopsy, the patient noted a blurring of vision. At the time of the initial examination at our hospital, his best-corrected visual acuity (BCVA) was 20/20 in both eyes but there were bilateral multiple Elschnig spots and sprinter hemorrhage at the fundus. Swept-source optical coherence tomography showed intra-retinal fluid, and serous retinal detachment (SRD). Fluorescein angiography revealed multiple punctate hyper fluorescences and indocyanine green angiography showed choroidopathy with increased vascular permeability. A general examination revealed symptoms of cardiac failure and multiple lymphadenopathies. Malignant hypertension with acute glomerulonephritis was diagnosed after a renal biopsy. After antihypertensive treatment, his blood pressure (BP) improved, and the SRD and choroidopathy promptly resolved. Presently, the patient is being followed up without complications. We report a case of hypertensive choroidopathy in a patient with CD associated with malignant hypertension. As a severe elevation in BP can damage choroidal vasculature and lead to vision loss, careful observation and active treatment are necessary.

The Efficacy of Golimumab Against Non-Infectious Uveitis: A PRISMA-Compliant Systematic Review and Meta-Analysis.

PURPOSE: In this PRISMA-compliant systematic review and meta-analysis, we aimed to assess the efficacy of golimumab (GOL) against non-infectious uveitis (NIU). METHODS: We included eight articles in the meta-analysis. The primary outcome was inflammation remission. Secondary outcomes were changes in the number of uveitis relapses/attacks, mean best-corrected visual acuity, central macular thickness, and systemic corticosteroid-sparing effects. RESULTS: In total, eight case series with 172 patients (43.6% female) were collected. Patients had 75% (95% CI: 56-87%) of remission; 42% (0.12-0.80) of patients showed improved visual acuity. The average central macular thickness decline was 38 µm (-56.51-18.54). The pooled results showed a significant decrease in the use of systemic corticosteroids. CONCLUSION: This study was limited by the use of non-RCT designs, limited sample sizes for outcomes, and heterogenetic underlying diseases. Our results suggest that GOL is effective against NIU. However, further evidence and analyses are required. (Funding: None; PROSPERO registration: CRD42021266214.).

Barium-induced toxic anterior segment syndrome.

Toxic anterior segment syndrome (TASS) is a rapid-onset inflammation of the eye following uneventful ocular surgery. We report a case of TASS following Baerveldt glaucoma implant (BGI) surgery. Inductively coupled plasma-mass spectrometry (ICP-MS) identified barium in the eye and in the eluate from the bleb of the BGI. We attribute TASS in our patient to the dissolution of barium from the BGI and its entry into the eye, where it causes severe inflammation.

Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.

Aim: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. Methods: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. Results: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. Conclusions: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.

Mitochondrial DNA as a Biomarker for Acute Central Serous Chorioretinopathy: A Case-Control Study.

Background: The literature suggests that stress may play a pivotal role in the precipitation of acute central serous chorioretinopathy (CSC) because chorioretinal integrity can be affected by the psychosocial state of the patient, indicating the need for a biomarker. Not only physical stress but also psychological stress causes many types of physical disorders. However, little is known about the pathophysiology of stress-induced disease. The objective of this study was to investigate whether serum factors might be involved in the development of stress-induced ocular diseases. Methods: This observational case series included 33 eyes of 33 consecutive patients with treatment-naïve acute CSC. Fifty eyes of 50 age-matched healthy volunteers were included in this study as non-CSC controls. Serum samples were collected from all participants, and the levels of mitochondrial DNA (mtDNA) were measured by quantitative real-time (RT)-PCR. Serum levels of high-mobility group box (HMGB) 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG), biological markers of acute/chronic inflammation and oxidative stress, were also measured. The relationships between serum mtDNA, 8-OHdG, and HMGB1 concentrations were investigated by multivariate regression analysis, alongside an assessment of clinical data. Results: In the treatment-naïve acute CSC group, the serum mtDNA levels (36.5 ± 32.4 ng/mL) were significantly higher than the levels in the control group (7.4 ± 5.9 ng/mL; p < 0.001). Serum levels of 8-OHdG and HMGB1 in treatment-naïve acute CSC patients measured 0.12 ± 0.08 ng/mL and 18.1 ± 35.0 ng/mL, respectively, indicating that HMGB1 levels were elevated in CSC compared with the control group. Multivariable regression analysis demonstrated that increased serum mtDNA levels were significantly associated with the height of serous retinal detachment. Conclusion: We showed serum mtDNA and HMGB1 level elevation and its relation to the clinical activities of CSC, indicating that serum mtDNA and HMGB1 could serve as biomarkers for the acute phase of the disease. The use of these biomarkers makes it possible to predict disease onset and determine disease severity.

Clinical Findings of Specular Microscopy Images in Cytomegalovirus Corneal Endotheliitis.

PURPOSE: The aim of this study is to evaluate the usefulness of specular microscopy as an alternative diagnostic tool for cytomegalovirus (CMV) corneal endotheliitis. DESIGN: A retrospective study. METHODS: One hundred and four patients with clinical manifestations of infectious corneal endotheliitis, iridocyclitis, and retinitis were included in this study. The presence of CMV deoxyribonucleic acid (DNA) was confirmed by multiplex polymerase chain reaction (PCR). Viral load was measured using real-time PCR. Corneal endothelium was observed by specular microscopy. The medical records and clinical manifestations of the patients were retrospectively reviewed and linked with the PCR results. RESULTS: Seventeen of 104 cases were CMV endotheliitis and/or iridocyclitis and had no history of intraocular surgery or corneal transplantation. There was a negative correlation between viral load and corneal endothelial cell counts. In 14 of 17 cases, owl's eye cells were observed by specular microscopy. The corneal endothelial cell counts were significantly reduced in the cases in which owl's eye cells were observed. CONCLUSIONS: In CMV endotheliitis, owl's eye cells were observed by specular microscopy with high probability (82%). Corneal endothelial cells significantly decreased when owl's eye cells were observed by specular microscopy. Specular microscopy represents a useful noninvasive auxiliary tool for diagnosing and monitoring CMV corneal endotheliitis.

Electrochemical Impedimetric Real-Time Polymerase Chain Reactions Using Anomalous Charge Transfer Enhancement.

We developed a new electrochemical impedimetric method for the real-time detection of polymerase chain reactions (PCR) based on our recent discovery that the DNA intercalator, [Ru(bpy)2DPPZ]2+, anomalously enhances charge transfer between redox mediators, K4[Fe(CN)6]/K3[Fe(CN)6], and a carbon electrode. Three mM [Fe(CN)6]3-/4- and 5 µM [Ru(bpy)2DPPZ]2+ were added to the PCR solution, and electrochemical impedance spectroscopy (EIS) measurements were performed at each elongation heat cycle. The charge transfer resistance (Rct) was initially low due to the presence of [Ru(bpy)2DPPZ]2+ in the solution. As PCR progressed, amplicon dsDNA was produced exponentially, and intercalated [Ru(bpy)2DPPZ]2+ ions, which could be detected as a steep Rct, increased at specific heat cycles depending on the amount of template DNA. The Rct increase per heat cycle, ΔRct, showed a peak at the same heat cycle as optical detection, proving that PCR can be accurately monitored in real time by impedance measurement. This simple method will enable a cost-effective and portable PCR device.

Novel corneal morphological alterations in Vogt-Koyanagi-Harada disease.

PURPOSE: To determine whether visual function, especially when dependent on the anterior segment of ocular tissue, is altered during high-dose steroid treatment for Vogt-Koyanagi-Harada disease (VKH). STUDY DESIGN: Retrospective case series METHODS: This case series included 18 eyes of 18 patients with VKH who received high-dose steroid therapy as initial treatment. All patients underwent anterior swept-source optical coherent tomography (CASIA-2) examinations during their clinical course to measure the central corneal thickness (CCT), average central corneal power (ACCP), maximum curvature (Kmax) and anterior chamber depth (ACD). RESULTS: The treatment duration was classified into the initial phase (earliest initial phase eIP; 0-1 month, initial phase: IP; 1-3months), middle phase (MP; 3-6 months), and late phase (LP; 6-9 months). The CCT decreased significantly after treatment (eIP vs. IP, p<0.01, eIP vs. MP, p<0.01; eIP vs. LP, p<0.01). The CCT at eIP was correlated with the flare value at 0M (R2=0.22). The change in Kmax at MP and LP was correlated with the flare value at 0M. Moreover, CCT at MP was correlated with rate of change in nasal angle open distance (AOD) at IP and rate of change in temporal AOD at IP. CONCLUSIONS: This study was the first to reveal morphological changes in the anterior segment of the eye in VKH using CASIA-2, which may affect visual acuity and the astigmatic axis. It is vital to assess corneal morphology to determine the cause of visual function deterioration in patients with VKH.

Diagnosis of Choroidal Disease With Deep Learning-Based Image Enhancement and Volumetric Quantification of Optical Coherence Tomography.

Purpose: The purpose of this study was to quantify choroidal vessels (CVs) in pathological eyes in three dimensions (3D) using optical coherence tomography (OCT) and a deep-learning analysis. Methods: A single-center retrospective study including 34 eyes of 34 patients (7 women and 27 men) with treatment-naïve central serous chorioretinopathy (CSC) and 33 eyes of 17 patients (7 women and 10 men) with Vogt-Koyanagi-Harada disease (VKH) or sympathetic ophthalmitis (SO) were imaged consecutively between October 2012 and May 2019 with a swept source OCT. Seventy-seven eyes of 39 age-matched volunteers (26 women and 13 men) with no sign of ocular pathology were imaged for comparison. Deep-learning-based image enhancement pipeline enabled CV segmentation and visualization in 3D, after which quantitative vessel volume maps were acquired to compare normal and diseased eyes and to track the clinical course of eyes in the disease group. Region-based vessel volumes and vessel indices were utilized for disease diagnosis. Results: OCT-based CV volume maps disclose regional CV changes in patients with CSC, VKH, or SO. Three metrics, (i) choroidal volume, (ii) CV volume, and (iii) CV index, exhibit high sensitivity and specificity in discriminating pathological choroids from healthy ones. Conclusions: The deep-learning analysis of OCT images described here provides a 3D visualization of the choroid, and allows quantification of features in the datasets to identify choroidal disease and distinguish between different diseases. Translational Relevance: This novel analysis can be applied retrospectively to existing OCT datasets, and it represents a significant advance toward the automated diagnosis of choroidal pathologies based on observations and quantifications of the vasculature.

Relationship between vitreoretinal lymphoma and the site of lymphoma development in the central nervous system.

PURPOSE: To investigate diffuse large B-cell lymphoma lesions with central nervous system (CNS) involvement in patients with vitreoretinal lymphoma (VRL) during long-term clinical courses. STUDY DESIGN: Multicenter, retrospective, and observational research. METHODS: Seventy-one patients participated in this study, 45 were newly diagnosed VRL patients with CNS involvement initially or during follow-up of at least 12 months. We identified the CNS lesions in the patients that had VRL and investigated whether the onset sites of the CNS lesions were associated with the VRL lesions or optic pathways. RESULTS: There were 42 patients with bilateral ocular lesions; 29 had unilateral lesions; 26 had incidental CNS lymphomas. Twenty patients developed recurrent CNS lymphoma 1-73 months after VRL diagnosis; 25 patients had no CNS lesions during the follow-up period. Most CNS lesions were in forebrain-originating tissues (95 lesions/total 124 CNS lesions total), followed by hindbrain-originating tissues, especially the cerebellum. Sixty-seven lesions were found in the non-optic pathway or non-visual cortex. CONCLUSION: Over 60% of the VRL patients had CNS lesions. CNS involvement was not associated with the optic pathway or visual cortex, suggesting that clinicians should carefully examine CNS lesions occurring in both forebrain- and hindbrain-originating tissues during a patient's clinical course. Moreover, the CNS lymphomas that manifest as VRL show multifocal tumor development.