Acute neuroretinitis as a delayed manifestation of tubulointerstitial nephritis and uveitis syndrome.

Purpose: Tubulointerstitial nephritis syndrome with uveitis (TINU) is a rare, acquired syndrome characterized by interstitial nephritis with bilateral uveitis. We report a case of TINU with typical bilateral anterior uveitis complicated by an atypical, delayed-onset neuroretinitis in a 12-year old patient. Observation: A 12-year-old female with a 21-month history of TINU featuring chronic bilateral anterior uveitis presented with one week of blurred vision in her left eye. On exam she was found to have new-onset disc edema in the right eye and neuroretinitis in the left eye. After a negative infectious disease workup, the patient was treated with a course of intravenous (IV) solumedrol with prednisone taper and advancement of her systemic immunosuppression. In follow up she demonstrated resolution of her disc edema and neuroretinitis with improved visual acuity and clinical exam. Conclusion: This case stresses the importance of monitoring for additional ocular manifestations including neuroretinitis years after the onset of anterior uveitis in TINU. In comparison to the two published cases of TINU with neuroretinitis, this case shares features of uveitis progression, and thus highlights the value of further description of TINU-associated neuroretinitis.

Prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of case-ascertained household cohort.

PURPOSE: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of case-ascertained household cohort. DESIGN: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling. METHODS: This analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity. RESULTS: Among the 83 SARS-CoV-2 infected participants, ten (12%) had at least one RNA positive tears specimen. Amongst these ten, five (50%) had concurrent presence of culturable virus, at a median of 7 days post symptom onset (IQR: 4-7 days) (absolute range: 4-8 days). CONCLUSIONS: In this longitudinal cohort, we found evidence of culturable virus in the tears of a small proportion of non-hospitalized SARS-CoV-2 infected individuals. Current public health infection precautions do not account for transmission via tears, so these findings may improve our understanding of potential sources of SARS-CoV-2 transmission and contribute to developing future guidelines.

Sjögren's Versus Non-Sjögren's Ocular Features: Similar Symptoms, But Significantly Worse Signs.

Purpose: To examine the ocular signs and symptoms in participants of the Sjögren's International Collaborative Clinical Alliance cohort, and to compare them across Sjögren's disease (SjD) status. Methods: Our study population comprised 3380 Sjögren's International Collaborative Clinical Alliance participants who had no missing data relevant to this study. Participants' SjD status was assessed using the updated 2016 American College of Rheumatism/European League Against Rheumatism SjD classification criteria. Participants completed baseline questionnaires of ocular symptoms and underwent ocular examinations. Differences in the ocular signs and symptoms between SjD and non-SjD groups were assessed. We used multivariable linear and linear mixed-effects models to investigate the impact of SjD on Ocular Surface Disease Index-6 and OSS. Results: Among 1532 participants classified as SjD, their Ocular Surface Disease Index-6 did not clinically differ from those classified as non-SjD (adjusted difference, -0.97; 95% confidence interval, -1.52 to -0.41). However, SjD participants exhibited an elevated ocular staining score (adjusted difference, 3.47; 95% confidence interval, 3.36-3.57; P < 0.001) compared with non-SjD participants. In addition, SjD was associated with increased odds of ocular signs, such as reduced tear break-up time, abnormal Schirmer I test, and corneal abnormalities, and was strongly related to more intense corneal and conjunctival staining, as well as additional corneal staining points. Conclusions: SjD is associated with a higher risk of ocular signs and pathology compared with non-SjD, whereas ocular symptoms remain similar. In addition, corneal abnormalities and corneal staining patterns could serve as a potential biomarker in identifying SjD-related dry eye.

Stromal Keratitis Associated With CMV Anterior Uveitis.

PURPOSE: Human cytomegalovirus (CMV) has commonly been reported as a cause of anterior uveitis and corneal endotheliitis. Unlike its other herpetic family members, herpes simplex virus and varicella zoster virus, involvement of the corneal stroma in CMV is uncommon. In this case series, we describe patients with CMV stromal keratitis. METHODS: This was a retrospective chart review of patients seen at a tertiary referral center from 1999 to 2023 with stromal keratitis who tested positive for CMV by directed polymerase chain reaction of aqueous fluid or corneal tissue. RESULTS: This series describes 5 patients, 4 of whom presented with anterior uveitis and stromal keratitis and were confirmed to be positive for CMV through the polymerase chain reaction of aqueous fluid. The fifth patient experienced recurrent corneal graft failures, with the most recent failed graft being positive for CMV based on immunohistochemical stains of the corneal stroma. The average age of patients was 62 years (range 36-80 years). Only 1 patient (20%) exhibited elevated intraocular pressure with stellate keratic precipitates at the initial presentation, whereas 3 other patients (60%) had a known history of glaucoma. CONCLUSIONS: Uveitis specialists are well aware of CMV as a cause of recurrent, hypertensive anterior uveitis but should also consider CMV in cases featuring stromal keratitis. The corneal endothelium may serve as a reservoir for both anterior uveitis and development of corneal stromal inflammation as demonstrated by the immunohistopathology exhibited in 1 case.

Association between Quality of Life and Visual Acuity in a Randomized Clinical Trial of Patients with Uveitis Taking Antimetabolites.

PURPOSE: To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites. METHODS: This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint. RESULTS: Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients = 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure. CONCLUSION: By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment.Abbreviations and Acronyms: QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95% CI = 95% confidence interval; MCID = minimal clinically important difference.

Risk factors for corneal abrasions in Nepal: a community-based study.

BACKGROUND: South Asia is experiencing rapid urbanization, which may be changing the risk factor profile for ocular trauma. The objective of this study was to compare risk factors for traumatic corneal abrasions in rural versus urban Nepal, and to assess if any risk factors were associated with a poor outcome. METHODS: In a prospective, cross-sectional, community-based study performed as part of a cluster-randomized trial, community health workers from Nepal were trained to diagnose and treat traumatic corneal abrasions. Participants with an abrasion were invited to complete a risk factor survey. The main exposure variable was the object of eye injury, stratified by rural-urban residence. The main outcome measure was a lack of corneal healing after a three-day course of antimicrobials. RESULTS: Of 3657 participants diagnosed with a corneal abrasion, 2265 completed a survey. Eye trauma occurred most frequently during agricultural activities. The most common object of injury was vegetative matter, accounting for approximately 40% of injuries in rural, peri-urban, and urban communities. Wood injuries were more common in rural communities (24%) compared with urban or peri-urban communities (13%). Eye injury from an animal was more likely to result in a non-healing corneal abrasion after 3 days of treatment compared with other types of trauma (prevalence ratio 2.59, 95%CI 1.16-5.76). CONCLUSIONS: Health promotion activities for prevention of corneal ulcers in Nepal should focus on agricultural trauma in both rural and urban areas. Community members experiencing eye trauma from an animal may benefit from early referral to an eye clinic.

Diagnostic accuracy of smartphone corneal photography for detection of corneal opacities in a resource-limited setting: a community-based study.

Purpose: To evaluate the diagnostic accuracy of smartphone corneal photography in detecting corneal opacities in a community-based setting. Methods: A case-control, diagnostic accuracy study was nested in a cluster-randomized trial of a corneal ulcer prevention intervention in Nepal. Smartphone corneal photography was performed annually on community members self-reporting a potential risk factor for a corneal infection. Corneal photographs were graded for the presence or absence of an opacity. All cases with an opacity on smartphone photography and an equal number of controls were invited for a comprehensive eye examination with a slit lamp biomicroscope at an eye hospital. A mobile team visited participants unable to come to the hospital, conducting a limited examination with a penlight. Results: Of 1332 study participants (666 cases and 666 controls), 1097 had a penlight examination (535 cases and 562 controls) and 191 had a slit lamp examination (120 cases and 71 controls). When penlight examination was considered the reference standard, smartphone diagnosis of a corneal opacity had a positive predictive value (PPV) of 47% (95% confidence interval 43-52%) and negative predictive value (NPV) of 95% (93-97%). When slit lamp examination was considered the reference standard, the overall PPV and NPV were 71% (62-78%) and 80% (70-88%), respectively. The NPV was greater for detection of opacities > 1mm, estimated at 95% (90-98%). Conclusions: Corneal photography performed in a resource-limited community-based setting using a smartphone coupled to an external attachment had acceptable diagnostic accuracy for detection of corneal opacities large enough to be clinically meaningful.

Anxiety and depression in patients with uveitis: a comprehensive review of observational studies.

PURPOSE OF THE REVIEW: The purpose of this review is to provide a comprehensive summary of observational studies evaluating anxiety and depression in patients with uveitis. RECENT FINDINGS: A higher prevalence of depression was reported in patients with uveitis compared to healthy controls in most observational studies. Symptoms of anxiety were often, but not always, significantly worse in patients with uveitis compared to controls. Most studies found that patients with uveitis had reduced vision-related quality of life that was associated with anxiety and depression symptoms. SUMMARY: Patients with uveitis have a higher risk of experiencing symptoms of depression and could benefit from screening and treatment. Preliminary screening for vision-related quality of life could also help determine if the patient requires assistance in mental health or other aspects of daily living.

Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.

BACKGROUND: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. MAIN BODY: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. CONCLUSION: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

Isolated Ocular Mpox without Skin Lesions, United States.

We report a case of a 53-year-old HIV-negative patient in San Francisco, California, USA, with no classic mpox prodromal symptoms or skin lesions who experienced fulminant, vision-threatening scleritis, keratitis, and uveitis. Deep sequence analysis identified monkeypox virus RNA in the aqueous humor. We confirmed the virus on the cornea and sclera by PCR.

Central Corneal Subbasal Nerve Plexus Abnormalities in Sjögren Disease: A Pilot Study.

PURPOSE: Small-fiber neuropathy (SFN) is known to be associated with Sjögren disease (SjD), and in vivo corneal confocal microscopy can identify features compatible with SFN. Here, we performed a descriptive study to identify features of SFN of the corneal subbasal nerve plexus using in vivo confocal microscopy. METHODS: We recruited 10 participants from the Sjögren's International Collaborative Clinical Alliance (SICCA), 1 new participant (in an effort to expand the SICCA cohort), and 22 healthy controls. All participants underwent slit-lamp examination and in vivo confocal microscopy of the central corneal subbasal nerve plexus centered about the central whorl to create a 30-image montage. Each image was analyzed with automated software (ACCmetrics, Manchester, United Kingdom) to produce 7 nerve metrics. We performed t-tests and age-adjusted regressions to make comparisons of nerve metrics between participants with SjD and healthy controls. RESULTS: Most nerve metrics were significantly lower in participants with SjD compared with healthy controls. The mean corneal nerve fiber density was found to be 3.5 mm/mm 2 in participants with SjD compared with 10.6 mm/mm 2 in healthy controls (95% confidence interval, -8.4 to -0.93; P = 0.02). Within the 11 participants with SjD, 22 eyes were analyzed on confocal microscopy, and 16 of those eyes (from 9 individuals) did not have an identifiable central whorl. Within the 22 healthy controls, 22 eyes (right eye alone) were analyzed on confocal microscopy, and 21 of those eyes had an identifiable central whorl. CONCLUSIONS: SjD exhibits lower corneal nerve metrics compared with healthy controls. These findings suggest that features compatible with SFN can distinguish SjD from healthy controls and may serve as a potential novel biomarker in identifying SjD.

Laboratory Investigations in Infectious Uveitis.

Laboratory investigations can play a significant role in the diagnosis and decision-making of infectious uveitis. Though direct demonstration of the infective organism remains the gold standard of diagnosis, it is not always possible with ocular tissues. Recent advancements in molecular techniques have made it possible to overcome these limitations and to identify the genomic DNA of pathogens associated with infectious uveitis. Techniques such as next-generation sequencing can analyze all DNA-based lifeforms, regardless of whether they are bacteria, fungi, viruses, or parasites and have been used in the laboratory diagnosis of intraocular inflammation. On the other hand, serological tests, though they dominate the diagnostic landscape of various infectious etiologies in uveitis in routine clinical practice, have varied specificities and sensitivities in different infectious uveitis. In this review, we focus on various methods of laboratory diagnosis of infectious uveitis and discuss the recent advances in molecular diagnosis and their role in various infectious clinical entities.

Reduced Dose Methotrexate and Mycophenolate Mofetil in Noninfectious Uveitis: A Sub-Analysis from the First-Line Antimetabolites as Steroid Sparing Therapy (FAST) Trial.

PURPOSE: Some patients taking methotrexate (MTX) or mycophenolate mofetil (MMF) experience intolerable side effects at full doses. We evaluated whether dose reduction affected treatment outcomes in uveitis patients. METHODS: Subanalysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial. Patients were randomized to receive MTX (25 mg weekly) or MMF (3 g daily). A pre-specified dose reduction protocol could be employed for intolerable side effects. Primary analysis was performed at 6 months. RESULTS: 43/194 patients (22%) required dose reduction. 88/151 patients (58%) on maximum doses and 32/43 patients (74%) on reduced doses were deemed treatment successes at 6 months. The odds ratio point estimate (1.60, 95% CI 0.72-3.74) favored dose-reduction but this was not significant. Following reduction, adverse events improved at the subsequent study visit (79 events reduced to 63 events). CONCLUSION: Dose reduction of antimetabolites was not associated with worse outcomes in this subanalysis of a uveitis trial.

Efficacy of the Fluocinolone Acetonide (Yutiq) Intravitreal Implant as Monotherapy for Uveitis.

PURPOSE: To evaluate the efficacy of the fluocinolone acetonide intravitreal implant (Yutiq) as monotherapy for uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients at a single academic health-care institution. METHODS: Medical record review of patients with non-infectious uveitis actively suppressed on an alternative anti-inflammatory regimen who received a fluocinolone acetonide implant. The primary outcome was continued control of inflammation based on clinical examination, optical coherence tomography, and fluorescein angiography. RESULTS: Thirteen patients (19 eyes) received an implant. Median follow-up was 6 months. Uveitis control was achieved in 14 eyes (74%), though three (21%) required a topical steroid after insertion. The remaining five eyes (26%) required additional intraocular treatments. CONCLUSION: The fluocinolone acetonide implant may not suffice as monotherapy for all patients with uveitis, but it may be effective as an adjunctive treatment. We propose a clinical workflow for the selection and treatment of patients who may benefit from it.

How Are Sicca Signs and Symptoms Associated With Depression Among Men Classified With and Without Sjögren Disease?

PURPOSE: Sjögren disease (SjD) cohorts represent rich resources to study associations between dry eye/mouth (sicca) signs/symptoms and depression. Because SjD affects mainly women, little is known about men with sicca signs/symptoms and associations with depression. The Sjögren's International Collaborative Clinical Alliance contained many men allowing for studying associations between sicca signs/symptoms and depression. We hypothesized that sicca symptoms would be positively associated with depression in males. DESIGN: Cross-sectional study. METHODS: At baseline, participants completed questionnaires and underwent ocular and oral examinations. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression models were used to identify associations between depression and SjD diagnostic criteria and sicca symptoms. RESULTS: Of 309 males, 98 were classified as SjD, whereas 198 were classified as non-SjD. We found that having a labial salivary gland biopsy with focus score ≥1 foci/mm2 was associated with a lower odds of being classified as depressed (odds ratio [OR]: 0.36, 95% CI: 0.18-0.73, P = .01). Having positive anti-Sjögren syndrome antigen A antibody was associated with lower odds of being classified as depressed (OR: 0.44, 95% CI: 0.23-0.88, P = .02). Higher odds of depression were found with ocular burning (OR: 3.16, 95% CI: 1.74-5.73, P < .001), light sensitivity (OR: 2.59, 95% CI: 1.48-4.55, P = .001), and complaints of dry mouth (OR: 4.58, 95% CI: 1.54-13.63, P = .006). CONCLUSION: Ophthalmologists should be specific when inquiring about ocular discomfort (focusing on burning and light sensitivity) and consider querying about depression and/or providing mental health resources to those who endorse such qualities.

Risk factors for corneal ulcers: a population-based matched case-control study in Nepal.

BACKGROUND/AIMS: We aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal. METHODS: This population-based matched case-control study was nested in a cluster randomised trial in 24 village development committees in Nepal. Incidence density sampling was used to match incident corneal opacity cases to controls, matching on time of opacity, age, sex and location. Cases and controls were invited to participate in a survey of risk factors for corneal ulcer. Risk factors were evaluated using conditional logistic regression to account for matching. RESULTS: Of the 540 participants with incident opacities identified in the trial, 433 were willing to participate in this substudy and matched to a control. Compared with controls, cases had lower odds of having any education vs no education (adjusted OR, aOR 0.60, 95% CI 0.39 to 0.94), working in non-manual labour occupations vs manual labour occupations (aOR 0.64, 95% CI 0.42 to 0.95) and preferring medical shops for ocular trauma versus eye care system centres (aOR 0.58, 95% CI 0.37 to 0.92). Cases had higher odds of protective goggle use versus no protection (aOR 3.8, 95% CI 1.3 to 11.0) and having an ocular injury vs none (aOR 7.7, 95% CI 4.3 to 13.6) compared with controls. CONCLUSION: We found ocular injury, manual labour and lower education to be strongly associated with the development of corneal ulcer. Given the persistent burden of corneal blindness in this area, prevention efforts could target efforts to increase access to care in areas where these factors are common.

Detection of Leptospirosis Genome from the Aqueous Humor of a Patient with Bilateral Uveitis.

BACKGROUND: Leptospira species are difficult to culture. Thus, when there is suspicion for an infectious etiology to uveitis, bacterial cultures may fail to identify Leptospira. We describe a case of leptospirosis-associated uveitis that evaded culture and molecular assays. DNA sequencing of the aqueous fluid showed the presence of Leptospira spp. METHODS: Retrospective case review of clinical and laboratory features of a patient with ocular leptospirosis is presented. RESULTS: DNA sequencing identified the genome of Leptospirosis spp. in the aqueous humor. CONCLUSION: Metagenomic sequencing, by virtue of its unbiased nature, can be a helpful adjunctive test when a strong clinical suspicion for intraocular infection persists despite negative routine culture and molecular assays.

Prevalence of Epstein-Barr Virus in Patients with Intraocular Inflammation.

The relationship between Epstein-Barr virus (EBV) infection and uveitis is unclear. We conducted an observational cross-sectional study to determine the prevalence of EBV in uveitis and to describe the clinical features of EBV-positive uveitis cases. This study was carried out at the F.I. Proctor Foundation at the University of California, San Francisco. All patients with suspected infectious uveitis who underwent unbiased metagenomic deep sequencing (MDS) were included. Demographics, testing information, and clinical features were documented. Eleven out of 288 patients with suspected infectious uveitis had EBV detected by RNA-seq in intraocular fluid. The prevalence of EBV in uveitis in our study sample is 4%. Three out of 11 EBV-positive eyes (27%) were found to have biopsy-proven vitreoretinal lymphoma. Future studies are needed to determine if EBV may drive the development of vitreoretinal lymphoma and if its presence should heighten the suspicion of vitreoretinal lymphoma.

Ocular Rosacea microBiome Study (ORBS)-sub-microbial versus antibiotic dosing of doxycycline versus placebo in treatment of symptomatic ocular rosacea: study protocol for a parallel-arm randomized clinical trial.

BACKGROUND: Ocular rosacea is common and is often managed with long-term antibiotic treatment. Doxycycline is the most commonly selected antibiotic for the treatment of rosacea. As there is no established standard of care treatment dose for rosacea, prescribed doses of doxycycline vary widely. The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily. However, this "sub-microbial" dose has never been evaluated in patients with ocular rosacea, and even the sub-microbial dose has potential to alter systemic mucosa flora. Here, we present a randomized controlled trial using RNA sequencing to fully characterize the impact of sub-microbial antibiotic dosing of doxycycline on antimicrobial resistance and bacterial composition of the ocular and gut flora. METHODS: In a triple-masked parallel randomized control trial, patients with ocular rosacea will be randomized to three arms: a 40-mg dose of doxycycline, a 200-mg antibiotic dose of doxycycline, or placebo. Collected rectal and lower eyelid samples will be compared for frequency of antimicrobial resistance genetic determinants and microbiome diversity. A subjective ocular surface disease index survey and objective tear breakup time measurement will be determined. DISCUSSION: These results will enhance our understanding of the overall systemic impact of long-term systemic sub-microbial antibiotic dosing for the treatment of chronic recurrent ocular inflammatory diseases. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.org (NCT05296837) on March 22, 2022.