@article {1586, title = {Association Between Baseline Macular Morphologic Features on Optical Coherence Tomography and Visual Outcomes in Patients with Vogt-Koyanagi-Harada Disease.}, journal = {Ocul Immunol Inflamm}, volume = {33}, year = {2025}, month = {2025 Feb}, pages = {263-270}, abstract = {

PURPOSE: The choroidal thickening and serous retinal detachments that characterize Vogt-Koyanagi-Harada (VKH) disease can be imaged in detail using spectral domain optical coherence tomography (SD-OCT). Whether specific qualitative and quantitative SD-OCT features at presentation were associated with visual outcomes in a randomized controlled trial comparing methotrexate to mycophenolate for steroid-sparing control of uveitis were evaluated.

METHODS: An exploratory subanalysis of data from the FAST trial in which SD-OCT images from VKH participants were analyzed for presence/absence of bacillary detachments, retinal pigment epithelium (RPE) folds, and internal limiting membrane (ILM) fluctuations was performed. A modified RPE undulation index was calculated to provide a quantifiable surrogate marker for choroidal folds.

RESULTS: SD-OCT images were available from 158 eyes with VKH. At baseline, bacillary detachments were present in 23.5\% of eyes, RPE folds in 22.8\% of eyes, and ILM fluctuations in 35.2\% of eyes. For each 0.1 unit increase in modified RPE undulation index, there was an associated 0.13 increase in mean logMAR BSCVA at baseline. None of the SD-OCT features were associated with BSCVA at the 6-month primary endpoint. Indeed, mean final BSCVA was similar in those with and without the SD-OCT features of interest at baseline, and was between 0.1 and 0.2 logMAR (Snellen visual acuity 20/25 to 20/30).

CONCLUSIONS: While eyes with VKH may present with a variety of SD-OCT imaging pathology prior to starting immunosuppression with methotrexate or mycophenolate mofetil, final visual outcome in our study was excellent. With appropriate immunosuppression, good visual outcomes are possible in VKH.ClinicalTrials.gov Identifier NCT01829295Date of Registration: April 11, 2013.

}, keywords = {Adult, Female, Fluorescein Angiography, Humans, Immunosuppressive Agents, Macula Lutea, Male, Methotrexate, Middle Aged, Mycophenolic Acid, Retinal Detachment, Retinal Pigment Epithelium, Tomography, Optical Coherence, Uveomeningoencephalitic Syndrome, Visual Acuity}, issn = {1744-5078}, doi = {10.1080/09273948.2024.2391420}, author = {Sundararajan, Miel and Rathinam, Sivakumar R and Thundikandy, Radhika and Kanakath, Anuradha and Balamurugan, S and Vedhanayaki, R and Miller, D Claire and Lim, Lyndell L and Suhler, Eric B and Al-Dhibi, Hassan A and Arellanes-Garcia, Lourdes and Reddy, Amit K and Feng, Shu and Doan, Thuy and Porco, Travis C and Shantha, Jessica G and Acharya, Nisha R and Gonzales, John A} } @article {1581, title = {Multiple Anterior Chamber Paracenteses May Be Needed to Identify Cytomegalovirus Anterior Uveitis.}, journal = {Am J Ophthalmol}, volume = {269}, year = {2025}, month = {2025 Jan}, pages = {189-194}, abstract = {

PURPOSE: To demonstrate cases of anterior uveitis requiring more than one anterior chamber paracenesis to elucidate CMV as the causative etiology.

DESIGN: Retrospective chart review.

METHODS: Patients were seen at the Francis I. Proctor Foundation at the University of California, San Francisco between 2013 and 2024. Patients who required more than one anterior chamber paracentesis to detect CMV as the etiologic agent of their anterior uveitis were included. Number of anterior chamber paracenteses required to detect CMV, demographic and clinical features, viral load at time of positive anterior chamber paracentesis and association between topical corticosteroid use and viral load at time of positive anterior chamber paracentesis.

RESULTS: Fourteen patients required a median of 2 (range 2-4) anterior chamber paracenteses to detect CMV. Mean age was 48.2 years, and 57.1\% were male. Most patients (64.3\%) were born in East and Southeast Asia. All affected eyes featured ocular hypertension. Five patients (35.7\%) were initially treated with systemic immunosuppression before CMV was detected. Increasing frequency of topical corticosteroid use was significantly associated with higher CMV viral loads (P \< .001). Five patients (35.7\%) required glaucoma surgery. In 13 patients with available data, uveitis was present for an average of 2776 days (range 23-7889 days) prior to CMV detection. Once diagnosed, most patients were treated with oral valganciclovir, with one patient transitioning to letermovir due to side effects.

CONCLUSIONS: CMV anterior uveitis may be more prevalent than previously recognized and often requires multiple anterior chamber paracenteses for diagnosis. Reliance on a signle negative test may lead to misdiagnosis and inappropriate treatment. Clinicians should maintain a high index of suspicion for CMV in cases of recurrent anterior uveitis, particularly in patients of East and Southeast Asian descent. This study highlights the importance of repeated testing and appropriate antiviral treatment to prevent complications such as glaucoma.

}, keywords = {Adult, Aged, Anterior Chamber, Antiviral Agents, Cytomegalovirus, Cytomegalovirus Infections, DNA, Viral, Eye Infections, Viral, Female, Glucocorticoids, Humans, Male, Middle Aged, Retrospective Studies, Uveitis, Anterior, Viral Load, Young Adult}, issn = {1879-1891}, doi = {10.1016/j.ajo.2024.08.025}, author = {Benador-Shen, Christine and Shantha, Jessica and Lee, Jennifer and Qian, Ying and Doan, Thuy and Gonzales, John A} } @article {101, title = {Association Between Noninfectious Uveitis and Psychological Stress.}, journal = {JAMA Ophthalmol}, volume = {137}, year = {2019}, month = {2019 02 01}, pages = {199-205}, abstract = {

Importance: Uveitis involves dysregulation of the ocular immune system. Stress has been shown to affect immune function, but it is unclear whether there is an association between stress and uveitis.

Objective: To determine whether having uveitis is associated with psychological stress.

Design, Setting, and Participants: A cross-sectional, case-control study including a self-administered survey, medical records review, and diurnal salivary cortisol test was conducted at a university-based uveitis clinic and comprehensive eye clinic. Participants included 146 consecutive adults with noninfectious uveitis and age-matched controls with no eye disease. The study was conducted from December 1, 2017, to March 14, 2018.

Main Outcomes and Measures: Participants completed the self-administered, Cohen 10-item Perceived Stress Scale (PSS-10), a demographics questionnaire. Responses to each question were categorized on a 5-point Likert scale, with total scores ranging from 0 (no stress) to 40 (high stress). In addition, participants submitted 3 salivary cortisol samples. Those with uveitis were classified as having recently active or controlled disease through medical records review. The prespecified primary analysis was a linear regression of PSS-10 score and uveitis correcting for age, sex, educational level, employment, and median income. Secondary analyses included comparing PSS-10 scores in patients with recently active and controlled uveitis, determining predictors of stress, and comparing diurnal salivary cortisol between uveitis and control groups.

Results: Of 146 eligible patients, 17 declined participation and 9 consented but were excluded because they did not complete both questionnaires, resulting in 120 patients (80 uveitis; 40 controls) in the final analysis. Eighty participants (66.7\%) were women, and 70 (58.3\%) were white. Median age was 40 years (interquartile range, 29-59 years). Having uveitis was associated with a 4.3-point increase in PSS-10 score (95\% CI, 1.8 to 6.9; P = .002). There was no significant difference in PSS-10 scores between patients with recently active and controlled uveitis (1.0 point greater for patients with active uveitis; 95\% CI, -2.0 to 3.9; P = .52). Factors associated with increased PSS-10 score in patients with uveitis included female sex (coefficient, 4.0; 95\% CI, 1.6 to 6.5; P = .002), current immunomodulatory therapy (coefficient, 2.5; 95\% CI, -0.3 to 5.2; P = .08), history of depression (coefficient, 3.8; 95\% CI, 0.8 to 6.8; P = .02), and having posterior or panuveitis (coefficient, 2.6; 95\% CI, 0.8 to 4.4; P = .006). Of the 70 participants (58.3\%) who had testable samples for cortisol analysis, diurnal salivary cortisol levels did not significantly differ between uveitis and nonuveitis groups.

Conclusions and Relevance: These findings suggest that patients with uveitis have higher levels of psychological stress compared with controls, yet no significant difference was identified in the stress of patients with active vs controlled uveitis. Consequently, comprehensive treatment for noninfectious uveitis may be able to address the psychological results of this disease.

}, keywords = {Adult, Case-Control Studies, Cross-Sectional Studies, Eye Infections, Female, Humans, Male, Middle Aged, Risk Factors, Stress, Psychological, Surveys and Questionnaires, Uveitis, Vision, Ocular, Visual Acuity}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2018.5893}, author = {Berlinberg, Elyse J and Gonzales, John A and Doan, Thuy and Acharya, Nisha R} } @article {96, title = {Association of Ocular Inflammation and Rubella Virus Persistence.}, journal = {JAMA Ophthalmol}, volume = {137}, year = {2019}, month = {2019 04 01}, pages = {435-438}, abstract = {

Importance: Metagenomic deep sequencing (MDS) demonstrates that persistent and active rubella virus (RV) infection is associated with Fuchs heterochromic iridocyclitis (FHI).

Objective: To assess the utility of MDS in identifying RV infection in patients with uveitis.

Design, Setting, and Participants: This case series assessed 6 patients diagnosed by MDS with RV-associated uveitis at a tertiary uveitis referral center in the United States.

Exposures: Prior RV infection.

Main Outcomes and Measures: Clinical examination findings, slitlamp photography, corneal confocal imaging, and infectious pathogen genome obtained from RNA sequencing.

Results: Six white men (age range, 36-61 years) were diagnosed with RV-associated uveitis by MDS. Three patients exhibited iris heterochromia associated with their uveitis in classic FHI fashion. The other 3 patients had less classic FHI features and exhibited anterior vitritis. Three patients had in vivo corneal confocal microscopy, with 2 demonstrating stellate keratic precipitates in addition to endothelial infiltration, spotlike holes, and enlarged intercellular boundaries. Of these 3 patients, 1 patient exhibited polymorphism and polymegathism of the endothelial cells.

Conclusions and Relevance: These findings suggest that persistent RV infection is associated with recurrent or chronic anterior or anterior-intermediate uveitis as well as corneal endothelial cell damage. Ophthalmologists should consider RV infection as a potential cause of hypertensive anterior and intermediate uveitis.

}, keywords = {Adult, Eye Infections, Viral, Humans, Male, Middle Aged, Rubella, Uveitis}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2018.6185}, author = {Gonzales, John A and Hinterwirth, Armin and Shantha, Jessica and Wang, Kaidi and Zhong, Lina and Cummings, Susie L and Qian, Ying and Wilson, Michael R and Acharya, Nisha R and Doan, Thuy} } @article {41, title = {Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis: A Randomized Clinical Trial.}, journal = {JAMA}, volume = {322}, year = {2019}, month = {2019 09 10}, pages = {936-945}, abstract = {

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective.

Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018.

Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109).

Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1\%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome.

Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5\%) women), 194 (89.8\%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7\%) patients in the methotrexate group vs 56 (57.1\%) in the mycophenolate group (difference, 9.5\% [95\% CI, -5.3\% to 21.8\%]; odds ratio [OR], 1.50 [95\% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4\%) in the methotrexate group vs 42 (55.3\%) in the mycophenolate group (difference, 19.1\% [95\% CI, 3.6\% to 30.6\%]; OR, 2.35 [95\% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3\%) in the methotrexate group vs 14 (63.6\%) in the mycophenolate group (difference, -30.3\% [95\% CI, -51.6\% to 1.1\%]; OR, 0.29 [95\% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0\%) in the methotrexate group and 8 patients (7.4\%) in the mycophenolate group.

Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.

Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.

}, keywords = {Adult, Anti-Inflammatory Agents, Drug Therapy, Combination, Enzyme Inhibitors, Female, Humans, Immunosuppressive Agents, Liver Function Tests, Male, Methotrexate, Middle Aged, Mycophenolic Acid, Prednisolone, Uveitis}, issn = {1538-3598}, doi = {10.1001/jama.2019.12618}, author = {Rathinam, S R and Gonzales, John A and Thundikandy, Radhika and Kanakath, Anuradha and Murugan, S Bala and Vedhanayaki, R and Lim, Lyndell L and Suhler, Eric B and Al-Dhibi, Hassan A and Doan, Thuy and Keenan, Jeremy D and Rao, Maya M and Ebert, Caleb D and Nguyen, Hieu H and Kim, Eric and Porco, Travis C and Acharya, Nisha R} } @article {116, title = {Time Trade-off Utility Values in Noninfectious~Uveitis.}, journal = {Am J Ophthalmol}, volume = {208}, year = {2019}, month = {2019 12}, pages = {47-55}, abstract = {

PURPOSE: To investigate time trade-off (TTO) utility values in patients with noninfectious uveitis and determine whether patient demographics and clinical characteristics are associated with utility scores.

DESIGN: Time trade-off utility analysis.

METHODS: Setting: A tertiary care uveitis center in San Francisco, California, USA.

PATIENT POPULATION: One hundred and four consecutive adults with noninfectious uveitis, enrolled between November 2016 and February 2017.

MAIN OUTCOME MEASURES: TTO utility values, as collected by an interviewer-guided survey. Information regarding general health, ocular symptoms, and religion was also collected and medical record review was conducted to record anatomic location of uveitis, disease activity, visual acuity, and treatments. Multivariable regression analysis with backward selection was used to identify variables associated with TTO values.

RESULTS: Median TTO score was 0.975 (interquartile range [IQR]: 0.8-1.0), corresponding to trading a median 1.28 years of remaining life for healthy eyes (IQR: 0-6.29). Regression analysis revealed that worse eye visual acuity, \>6\ months of oral corticosteroid use, and current antidepressant use were associated with lower TTO scores (P\ = .008, P\ = .006, P\ = .008, respectively), controlling for age and sex. In particular, patients who had been taking oral corticosteroids for more than 6\ months, regardless of dose, were 10.5 times more likely to trade 20\% or more years of remaining life (TTO <=0.8) than patients not taking oral corticosteroids (95\% confidence interval: 2.3, 48.1; P\ = .002).

CONCLUSIONS: Patients with noninfectious uveitis had measurable, though modest, reductions in quality of life, as assessed by TTO, and these decreases were significantly associated with visual acuity in the worse eye and long-term oral corticosteroid use.

}, keywords = {Administration, Oral, Adult, Antidepressive Agents, Cross-Sectional Studies, Female, Glucocorticoids, Health Status, Health Surveys, Humans, Male, Middle Aged, Quality of Life, Sickness Impact Profile, Surveys and Questionnaires, Tertiary Care Centers, Uveitis, Visual Acuity}, issn = {1879-1891}, doi = {10.1016/j.ajo.2019.06.005}, author = {Niemeyer, Katherine M and Gonzales, John A and Doan, Thuy and Browne, Erica N and Rao, Maya M and Acharya, Nisha R} } @article {146, title = {When to Consider Bisphosphonates in Patients on Steroids for Chronic Ocular Inflammatory Conditions.}, journal = {J Ocul Pharmacol Ther}, volume = {35}, year = {2019}, month = {2019 09}, pages = {379-380}, keywords = {Adrenal Cortex Hormones, Adult, Aged, Aged, 80 and over, Bone Density Conservation Agents, Diphosphonates, Eye Diseases, Female, Humans, Male, Middle Aged, Osteoporotic Fractures}, issn = {1557-7732}, doi = {10.1089/jop.2019.0058}, author = {Takhar, Jaskirat S and Pawar, Varun K and Marneris, Athanasios G and Thuy A Doan and Acharya, Nisha R and Gonzales, John A} }