Cytomegalovirus Corneal Endotheliitis: A Comprehensive Review.

Cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis are the most common ocular diseases caused by CMV infections in immunocompetent patients. The incidence of CMV corneal endotheliitis is relatively high in middle-aged men. CMV corneal endotheliitis presents with mild anterior chamber inflammation, corneal edema, keratic precipitates, and elevated intraocular pressure. It resembles Posner-Schlossman syndrome and Fuchs uveitis because of the elevated intraocular pressure. Without proper diagnosis and treatment, it may progress to bullous keratopathy or glaucoma, necessitating keratoplasty or glaucoma surgery. Therefore, early diagnosis and treatment are important for a good prognosis. Aqueous humor analysis can facilitate the diagnosis of CMV corneal endotheliitis, and early antiviral treatment can decrease the risk of corneal compensation or glaucomatous optic atrophy. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of CMV corneal endotheliitis along with the evidence for early clinical diagnosis and active antiviral treatment.

The Role of Corticosteroids and Immunomodulatory Therapy in the Management of Infectious Uveitis.

PURPOSE: The index review aims to provide an update on the role of corticosteroids and steroid-sparing immunomodulatory therapy (IMT) in managing patients with infectious uveitis. METHOD: Narrative literature review. RESULTS: Corticosteroids and immunomodulatory therapy (IMT) focus on the host defense system instead of the pathogen, adjusting exaggerated inflammatory reactions to reduce potential harm to ocular tissues. Systemic or local corticosteroids are primarily selected as adjunctive medication for infectious uveitis. Concomitant corticosteroids have also been used in cases of paradoxical worsening in ocular tuberculosis and immune recovery uveitis in cytomegalovirus (CMV) retinitis. While there is no well-established evidence to support the use of IMT in infectious uveitis, it is occasionally used in clinical settings to treat persistent inflammation following resolution of infection such as cases of ocular tuberculosis and ocular syphilis where an insufficient response is observed with corticosteroids. CONCLUSION: There is no consensus on the position of immunomodulatory therapy in the management of infectious uveitis with different etiologies. The index review provides an overview of available adjunctive corticosteroids and IMT options to assist clinicians in managing such disease entities more efficiently.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis.

AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2-global current practice patterns for the management of Cytomegalovirus anterior uveitis.

AIMS: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide. METHODS: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform. RESULTS: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts). CONCLUSIONS: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.

Recent advances in uveitis therapy: focus on selected phase 2 and 3 clinical trials.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.

Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

Association of a Bioimpedance Profile with Optical Coherence Tomography Features in Diabetic Macular Edema.

We examined the association between bioimpedance profiles and optical coherence tomography (OCT) features in patients with diabetic macular edema (DME). This cross-sectional study included 100 eyes of 100 patients with type 2 diabetes mellitus. The systemic fluid status was assessed using extracellular water-to-total body water ratio (ECW/TBW) and phase angle (PhA), which was measured using bioimpedance equipment. ECW/TBW was higher in the DR (diabetic retinopathy) with DME group than in the no DR and DR without DME groups (p = 0.007 and p = 0.047, respectively); however, no significant difference was observed between the no DR and DR without DME groups. The PhA values were significantly lower in the DR with DME group (5.45 ± 0.84) than in the no DR (6.69 ± 0.69) and DR without DME groups (6.05 ± 1.15) (p < 0.001, p = 0.032, respectively). The presence of multiple HRF (hyper-reflective foci) was associated with a significantly higher ECW/TBW (p = 0.001). In the group with the most significant HRF, PhA was lower than in those with none or moderate amounts of HRF (p < 0.05). Bioimpedance fluid profiles of patients with OCT features of DME suggest a connection between the overall systemic state, including fluid status and DME development. Further research is required to fully understand and utilize this information for effective clinical assessment and treatment planning.

Evaluating the Diagnostic Accuracy and Management Recommendations of ChatGPT in Uveitis.

INTRODUCTION: Accurate diagnosis and timely management are vital for favorable uveitis outcomes. Artificial Intelligence (AI) holds promise in medical decision-making, particularly in ophthalmology. Yet, the diagnostic precision and management advice from AI-based uveitis chatbots lack assessment. METHODS: We appraised diagnostic accuracy and management suggestions of an AI-based chatbot, ChatGPT, versus five uveitis-trained ophthalmologists, using 25 standard cases aligned with new Uveitis Nomenclature guidelines. Participants predicted likely diagnoses, two differentials, and next management steps. Comparative success rates were computed. RESULTS: Ophthalmologists excelled (60-92%) in likely diagnosis, exceeding AI (60%). Considering fully and partially accurate diagnoses, ophthalmologists achieved 76-100% success; AI attained 72%. Despite an 8% AI improvement, its overall performance lagged. Ophthalmologists and AI agreed on diagnosis in 48% cases, with 91.6% exhibiting concurrence in management plans. CONCLUSIONS: The study underscores AI chatbots' potential in uveitis diagnosis and management, indicating their value in reducing diagnostic errors. Further research is essential to enhance AI chatbot precision in diagnosis and recommendations.

Investigating mental rehearsal's applicability in guiding independent E-learning (IMAGINE) of eye examination skills during the pandemic.

BACKGROUND: COVID-19's infection control policies have hindered the Deliberate Practice of clinical examinations. Guided Mental Rehearsal (GMR) may overcome this obstacle by facilitating independent, repetitive practice. Underpinned by the 'Motor Simulation Theory,' GMR reinforces similar neuro-circuit activations during physical practice and was proven effective in surgical training. METHODS: This prospective, randomized controlled study evaluated the efficacy of GMR versus 'peer-learning' of Confrontational Visual Field Examination (CVFE). Third-year medical-students without clinical Ophthalmology experience were recruited. Controls (n = 40) watched an e-learning instructional video (8-min CVFE tutorial) followed by 6-min of 'peer-learning.' GMR-students (n = 40) had 'peer-learning' replaced by a 6-min GMR audio-recording (CVFE running commentary). Pre-test and post-test MCQs were administered to determine baseline knowledge and knowledge acquisition, respectively. 28 controls and 26 GMR-students performed CVFE on simulated patients with right homonymous hemianopia. Four Ophthalmologists graded their performances using a checklist-based marking scheme. RESULTS: Both groups did not exhibit a significant difference in pre-test scores (8.550 vs. 7.947, p = 0.266); outcome of sub-group analysis of CVFE-performing candidates was similar (8.214 vs. 7.833, p = 0.561). Post-test scores were significantly higher than pre-test in both groups (all p < .001), without inter-group difference (14.000 vs. 15.000, p = 0.715). GMR-group had significantly higher scores on CVFE performance than controls (85.354 vs. 73.679%, p = .001). CONCLUSIONS: GMR improved psychomotor but not cognitive aspect of learning CVFE. This may be attributable to GMR's theoretical resemblance with physical practice, with additional expert guidance. By enabling independent learning, GMR may also reduce the demand for teaching manpower and thus education cost in the future.

Clinical characteristics and treatment outcomes of cytomegalovirus anterior uveitis and endotheliitis: A systematic review and meta-analysis.

Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45-98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21-0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74-100% and 95%, 95% CI 88-100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5-2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences.

Antiviral Therapy for Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV)-Induced Anterior Uveitis: A Systematic Review and Meta-Analysis.

Topic: Herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common ocular pathogens associated with infectious anterior uveitis. Currently, there are a number of antiviral agents administered to treat viral anterior uveitis (VAU). However, there is no consensus or guidelines about the most appropriate approach leading for the best treatment outcomes with fewer ocular complications. Clinical Relevance: To perform a systematic review and meta-analysis of the efficacy of different antiviral therapies in the management of anterior uveitis secondary to HSV and VZV. Methods: We searched PubMed, Web of Science, CINAHL, OVID, and Embase up to January 2020. Randomized trials, non-randomized intervention studies, controlled before and after studies and observational studies assessing the effect of oral and or topical treatments for VAU were considered. Data extraction and analysis with evaluation of the risk of bias in the included trials were performed. Results: Oral acyclovir demonstrated a statistically significant good treatment outcome in the management of VZV anterior uveitis (vs. placebo) (OR 0.26, 95% CI 0.11-0.59), but did not have similar effect in HSV anterior uveitis (OR 0.47, 95% CI 0.15-1.50). In the treatment of VZV anterior uveitis, there was significant superiority of oral acyclovir-7 day course-over topical acyclovir (OR 4.17, 95% CI 1.28-13.52). Whereas, there was no significant superiority of one of the following treatment regimens over the others: topical acyclovir over topical corticosteroids (OR 1.86, 95% CI 0.67-5.17), and oral acyclovir-7 day course-over oral acyclovir-14 day course-(OR 0.21, 95% CI 0.01-4.50) or oral valaciclovir (OR 1.40, 95% CI 0.48-4.07). Conclusion: Treatment of HSV and VZV anterior uveitis is currently based on individual experiences and limited literature, largely due to weak clinical trial evidence in this regard. Our results highlight the existence of a substantial gap in our evidence base. This finding might contribute to future research studies to ascertain the role of different antiviral therapies in the treatment of VAU. Systematic Review Registration: PROSPERO registration number: CRD420202 00404.

BISPHOSPHONATE-INDUCED BILATERAL ANTERIOR UVEITIS AND CHOROIDAL EFFUSIONS WITH SECONDARY ANGLE CLOSURE.

PURPOSE: To report a case of bisphosphonate-induced bilateral anterior uveitis and choroidal effusions with secondary angle closure in a 64-year-old female patient. METHODS: Observational case report. RESULTS: A 64-year-old woman with history of scleroderma and antiphospholipid syndrome, presented with bilateral painless blurring of vision after commencement of alendronate. Clinical examination revealed bilateral anterior uveitis and choroidal effusions with resultant secondary angle closure in the left eye. Ultrasound biomicroscopy showed bilateral anteriorly rotated ciliary bodies. There was also a -2D myopic shift in the left eye. On drug cessation, complete resolution was seen within 2 weeks. CONCLUSION: In the absence of other plausible etiologies and with recent commencement of a new drug, we postulate that the anterior uveitis and choroidal effusions are likely due to alendronate. This is further supported by complete resolution of the inflammation and effusions once alendronate was withheld.

COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.

Usage of glaucoma-specific patient-reported outcome measures (PROMs) in the Singapore context: a qualitative scoping exercise.

BACKGROUND: Despite the increasing emphasis on the role of glaucoma-specific patient-reported outcome measures (PROMs) as relevant outcome measures for the impact of glaucoma and its intervention on patients' daily lives, the feasibility of implementing PROMs in the routine clinical setting in Singapore remains undefined. We aim to evaluate the comprehensibility, acceptability, and relevance of four glaucoma-specific PROMs at healthcare professionals' and patients' level in a Singapore context. METHODS: Sixteen ophthalmic healthcare professionals and 24 glaucoma patients, with average age 60 years (SD = 15), were invited from a tertiary hospital in Singapore. Semi-structured interviews were conducted to explore participants' perceptions on the content and administration of four glaucoma-specific PROMs - the Glaucoma Quality of Life-15, Glaucoma Symptom Identifier, Independent Mobility Questionnaire and Treatment Satisfaction Survey of Intra-ocular Pressure. Semi-structured interviews were hand transcribed, and analysed thematically. Each participant filled out a feasibility survey at the end of interview. RESULTS: 79% of glaucoma patients and 94% of glaucoma healthcare professionals felt selected PROMs relevant to patients. 63% of glaucoma patients and 50% of healthcare professionals felt that selected PROMs were sufficiently comprehensive for clinical use. 46% of glaucoma patients and 56% of healthcare professionals felt selected PROMs were user-friendly. CONCLUSIONS: Using PROMs in the Singapore clinical setting receives promising support from both healthcare professionals and patients. The identified potential barriers tailored to Singapore clinical setting will help successful implementation of PROMs into routine clinical care.