TM4SF19 controls GABP-dependent YAP transcription in head and neck cancer under oxidative stress conditions.

Tobacco and alcohol are risk factors for human papillomavirus-negative head and neck squamous cell carcinoma (HPV- HNSCC), which arises from the mucosal epithelium of the upper aerodigestive tract. Notably, despite the mutagenic potential of smoking, HPV- HNSCC exhibits a low mutational load directly attributed to smoking, which implies an undefined role of smoking in HPV- HNSCC. Elevated YAP (Yes-associated protein) mRNA is prevalent in HPV- HNSCC, irrespective of the YAP gene amplification status, and the mechanism behind this upregulation remains elusive. Here, we report that oxidative stress, induced by major risk factors for HPV- HNSCC such as tobacco and alcohol, promotes YAP transcription via TM4SF19 (transmembrane 4 L six family member 19). TM4SF19 modulates YAP transcription by interacting with the GABP (Guanine and adenine-binding protein) transcription factor complex. Mechanistically, oxidative stress induces TM4SF19 dimerization and topology inversion in the endoplasmic reticulum membrane, which in turn protects the GABPß1 subunit from proteasomal degradation. Conversely, depletion of TM4SF19 impairs the survival, proliferation, and migration of HPV- HNSCC cells, highlighting the potential therapeutic relevance of targeting TM4SF19. Our findings reveal the roles of the key risk factors of HPV- HNSCC in tumor development via oxidative stress, offering implications for upcoming therapeutic approaches in HPV- HNSCC.

Changes in the incidence of optic neuritis before and after COVID-19: A nationwide study 2017-2022.

PURPOSE: To determine the risk of optic neuritis (ON) during non-pharmaceutical interventions (NPI), vaccination and infection phase of coronavirus disease-19 (COVID-19) in comparison to pre-outbreak levels in pediatric and adult populations in South Korea. DESIGN: A nationwide, population-based, retrospective study. PARTICIPANTS: South Korean individuals with a primary diagnosis of ON between January 2017 and December 2022. METHODS: The Korean Health Insurance Review and Assessment database was queried for new diagnoses of ON between January 2017 and December 2022. Data were divided into 4 periods: pre-COVID-19 (2017-2019), NPI (2020), nationwide vaccination (2021) and nationwide infection (2022). The risk of ON development for each period was calculated and compared to pre-COVID-19 levels with 95% confidence intervals (CI) reported. MAIN OUTCOME MEASURES: Incidence rate ratio (IRR) of ON for each period. RESULTS: A total of 7,216 patients (52.7 % females) were included in the study, with 3,770 patients diagnosed with ON pre-COVID-19 (2017-2019), 1,193 patients during NPI, 1,135 patients during the vaccination and 1,118 patients during the infection phases. The annual incidence of ON during NPI (IRR 0.92 (95% CI 0.85-1.00), P=0.043), vaccination (IRR 0.88 (95% CI 0.81-0.95), P=0.001) and infection (IRR 0.86 (95% CI 0.80-0.93), P<0.001) phases significantly decreased compared to pre-COVID-19 levels when adjusted for age and sex. The proportions of diagnosis with multiple sclerosis (MS), neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM) among patients who developed ON significantly increased in 2021 in comparison to the pre-outbreak levels (9.87% vs. 5.81%; P=0.0002). CONCLUSIONS: The risks of ON development during NPI, vaccination and infection phases of COVID-19 did not increase in comparison to the pre-outbreak levels in general population. However, COVID-19 vaccination may be associated with increased risks of ON associated with diseases such as ADEM, MS and NMOSD.

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination.

PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Exploring the Challenges of Distinguishing Punctate Inner Choroidopathy from Multifocal Choroiditis and Panuveitis.

PURPOSE: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria. METHODS: Using the medical records of the patients, we reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on SUN criteria and compared the result to the clinical diagnosis. RESULTS: Of 100 eyes, 29 eyes (29%) were diagnosed as PIC and 15 eyes (15%) were diagnosed as MCP using SUN criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed PIC eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using SUN criteria. CONCLUSIONS: The existing diagnostic criteria showed limitations in capturing all clinical cases of PIC or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia, could be considered to enhance diagnostic accuracy.

Genome-wide RNA interference screening reveals a COPI-MAP2K3 pathway required for YAP regulation.

The transcriptional regulator YAP, which plays important roles in the development, regeneration, and tumorigenesis, is activated when released from inhibition by the Hippo kinase cascade. The regulatory mechanism of YAP in Hippo-low contexts is poorly understood. Here, we performed a genome-wide RNA interference screen to identify genes whose loss of function in a Hippo-null background affects YAP activity. We discovered that the coatomer protein complex I (COPI) is required for YAP nuclear enrichment and that COPI dependency of YAP confers an intrinsic vulnerability to COPI disruption in YAP-driven cancer cells. We identified MAP2K3 as a YAP regulator involved in inhibitory YAP phosphorylation induced by COPI subunit depletion. The endoplasmic reticulum stress response pathway activated by COPI malfunction appears to connect COPI and MAP2K3. In addition, we provide evidence that YAP inhibition by COPI disruption may contribute to transcriptional up-regulation of PTGS2 and proinflammatory cytokines. Our study offers a resource for investigating Hippo-independent YAP regulation as a therapeutic target for cancers and suggests a link between YAP and COPI-associated inflammatory diseases.

Complications, treatments, and visual prognosis of choroidal osteomas.

PURPOSE: This study aims to report complications, treatments, and visual prognosis of choroidal osteoma. METHODS: We retrospectively reviewed electronic medical records and multimodal images of 41 patients with choroidal osteoma. RESULTS: Visually significant complications included choroidal neovascularization (CNV) in 21 (47.7%) eyes and subretinal fluid (SRF) without CNV in 14 (31.8%) eyes. The most common treatment was intravitreal anti-vascular endothelial growth factor (VEGF) injection: 13 (61.9%) eyes with CNV received an average of 6.3 injections, and 6 (42.9%) eyes with SRF but without CNV received 1.8 injections. As the first-line treatment, intravitreal anti-VEGF injection induced complete or partial remission in 93.4% of eyes with CNV and 57.1% of eyes with SRF. The probability of legally low vision estimated at 3 and at 5 years was 29.1% and 34.2%, respectively. The presence of CNV and outer retinal tubulation (ORT) was independent risk factors for vision loss (adjusted odds ratio, 8.08 and 6.94, respectively). CONCLUSIONS: The development of CNV and ORT was strong risk factors for visual impairment. Due to the frequent recurrence of complications and poor visual prognosis, regular check-ups and appropriate treatment choices are warranted.

Factors associated with ocular adverse event after immune checkpoint inhibitor treatment.

Ocular adverse events (OAEs) including vision-threatening intraocular inflammation after immune checkpoint inhibitor (ICI) treatment have been increasingly reported; however, the risk factors associated with OAEs remain elusive. Here, we determined the factors associated with OAEs after ICI treatment. We analyzed 40 consecutive patients who experienced OAEs after ICI treatments. The OAEs included anterior uveitis, chorioretinitis, papillitis, foveal interdigitation zone thickening/serous retinal detachment (IZT/SRD), retinal vascular occlusion, and strabismus and ptosis. Of 40 patients, 18 (45%) were treated with atezolizumab, 13 (33%) with pembrolizumab, 7 (18%) with nivolumab, 1 (3%) with ipilimumab/nivolumab, and the other 1 (3%) with durvalumab/tremelimumab. BRAF/MEK inhibitors were concurrently used in 19 (48%) patients. Occurrence of intraocular inflammation was significantly associated with previous ocular surgery and trauma history (P = 0.015) and pembrolizumab use (P = 0.031). Neuro-ophthalmic complications and IZT/SRD were associated with brain metastasis (P = 0.005) and treatment with BRAF/MEK inhibitor (P < 0.001), respectively. In extensive literature review for clinical cases, we identified seven cases with intraocular inflammation, which were not observed with ipilimumab treatment, that occurred after a change of the drug to pembrolizumab. Collectively, these findings provide better understandings of OAEs after ICI treatment.

Therapeutic perspectives for structural and functional abnormalities of cilia.

Ciliopathies are a group of hereditary disorders that result from structural or functional abnormalities of cilia. Recent intense research efforts have uncovered the genetic bases of ciliopathies, and our understanding of the assembly and functions of cilia has been improved significantly. Although mechanism-specific therapies for ciliopathies have not yet received regulatory approval, the use of innovative therapeutic modalities such as oligonucleotide therapy, gene replacement therapy, and gene editing in addition to symptomatic treatments are expected to provide valid treatment options in the near future. Moreover, candidate chemical compounds for developing small molecule drugs to treat ciliopathies have been identified. This review introduces the key features of cilia and ciliopathies, and summarizes the advances as well as the challenges that remain with the development of therapies for treating ciliopathies.

Characterization of Ginkgo biloba Leaf Flavonoids as Neuroexocytosis Regulators.

Ginkgo biloba leaf (GBL) is known as a potential source of bioactive flavonoids, such as quercetin, arresting the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-zippering. Here, the GBL flavonoids were isolated in two different manners and then examined for their bioactivity, physicochemical stability, and biocompatibility. The majority of flavonoids in the non-hydrolyzed and acidolyzed isolates, termed non-hydrolyzed isolate (NI) and acidolyzed isolate (AI) hereafter, were rich in flavonol glycosides and aglycones, respectively. Glycosidic/aglyconic quercetin and kaempferol were abundant in both NI and AI, whereas a little of apigenin, luteolin, and isorhamnetin were found in AI. NI was more thermostable in all pH ranges than quercetin, kaempferol, and AI. NI and AI both inhibited neurotransmitter release from differentiated neuronal PC-12 cells. NI and AI showed 1/2-1/3 lower EC50/CC50 values than quercetin and kaempferol. The NI and AI exhibited no toxicity assessed by the tests on chorioallantoic membranes of hen's eggs, removing toxicological concerns of irritation potential. Moreover, GBL isolates, particularly AI, showed antioxidant and anti-inflammatory activities in the use below the CC50 levels. Taken together, these results suggest that GBL isolates that are rich in antioxidant flavonoids are effective anti-neuroexocytotic agents with high stability and low toxicity.

INCIDENCE OF AND RISK FACTORS FOR DISSOCIATED OPTIC NERVE FIBER LAYER AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To investigate the incidence of and risk factors for a dissociated optic nerve fiber layer (DONFL) after epiretinal membrane surgery. METHODS: Two hundred and ninety-six primary pars plana vitrectomy operations for epiretinal membrane that were eligible for inclusion in the study. All patients received a complete ophthalmologic examination and color fundus photography, optical coherence tomography preoperatively and postoperatively. DONFL group and non-DONFL group was compared. Univariate and multivariate analyses were performed to establish the risk factors for DONFL. RESULTS: A DONFL developed in 30 of the 296 eyes (incidence, 10.1%). Internal limiting membrane (ILM) peeling was performed in 29 of 30 eyes (96.7%) in the DONFL group and 126 of 266 eyes (47.4%) in the control group (P < 0.001). Intravitreal gas tamponade was performed in 21 eyes (70.0%) in the DONFL group and 133 eyes (50.0%) in the control group (P = 0.038). The ILM peeling (odds ratio, 32.22 [4.33-240.0]; P = 0.001) and intravitreal gas tamponade (odds ratio, 2.33 [1.03-5.28]; P = 0.042) were significantly associated with DONFL. CONCLUSION: It was found that ILM peeling and intravitreal gas tamponade were correlated with postoperative DONFL. The ILM peeling with intravitreal gas tamponade was more strongly correlated with postoperative DONFL formation than was ILM peeling alone.

Granulicatella elegans Causing Periorbital Infection During Orthodontic Treatment.

Granulicatella elegans is a normal component of the oral flora and is an unusual causative agent of infective endocarditis. A case of G. elegans periorbital infection of the eyelid after dental treatment is reported. A healthy 35-year-old man presented with painful swelling of the left upper eyelid. He was empirically treated with oral amoxicillin for 1 week. He presented 3 months later with the same clinical features. G. elegans and Staphylococcus epidermidis were identified in bacterial cultures from wound aspirates. Probable relapse of periorbital infection was successfully treated with a 6-week course of oral amoxicillin. This is the first reported case of a non-bloodstream infection caused by G. elegans. Clinicians should be aware of G. elegans as an unusual causative agent of periorbital infection. Within the limitations of this case report, prolonged antibiotic therapy is recommended for a G. elegans periorbital infection to minimize the risk of relapse.

FLUCTUATION OF INFUSION PRESSURE DURING MICROINCISION VITRECTOMY USING THE CONSTELLATION VISION SYSTEM.

PURPOSE: To measure fluctuations in infusion pressure and intraocular pressure (IOP) during vitrectomy performed using a flow-based IOP control system. METHODS: Using 3 vitrectomized porcine eyes, the authors simultaneously measured infusion pressure and IOP during vitreous cutting and aspiration and after extraction of operative instruments in 23-gauge and 25-gauge system. The measurements were performed with the "IOP control" setting turned on or off. The efficacy of valved cannula and a built-in "IOP control limit" module in attenuation of infusion pressure fluctuation was evaluated. RESULTS: At set pressure of 30 mmHg and 60 mmHg, the mean infusion pressure levels were 43.7 mmHg and 78.7 mmHg in the vitreous cutting mode, 67.4 mmHg and 101.2 mmHg in the aspiration mode, and 72.8 mmHg and 115.8 mmHg after extraction of the operative instrument, respectively, when the 23-gauge system was used. Use of valved cannulas effectively attenuated fluctuations in both infusion pressure and IOP. When the IOP control limit setting was "on," the compensatory infusion pressure increase was markedly limited and similar to the set pressure level when the IOP control limit was set at Level 2. Similar results were obtained when a 25-gauge system was used. CONCLUSION: Infusion pressure increased markedly during vitrectomy using a flow-based IOP control system.

CLINICAL COURSE OF DIABETIC RETINOPATHY IN KOREAN TYPE 2 DIABETES AFTER BARIATRIC SURGERY: A Pilot Study.

PURPOSE: To assess the changes in diabetic retinopathy (DR) in Type 2 diabetes (T2DM) patients after bariatric surgery. METHODS: Consecutive 20 patients with T2DM who underwent bariatric surgery and were followed for at least 12 months were enrolled. The case history was reviewed retrospectively, and laboratory data were assessed at baseline and every 3 months postoperatively. Two retinal specialists evaluated the severity of DR with dilated fundus examination preoperatively and postoperatively. Factors associated with DR progression were assessed. RESULTS: During the follow-up period, 2 of 12 patients without DR and 2 of 3 patients with mild nonproliferative DR before surgery developed moderate nonproliferative DR. All five patients with moderate nonproliferative DR or worse preoperatively had progression requiring intervention. Preexisting DR (P = 0.005) and albuminuria (P = 0.01) were identified as associated with DR progression. Six patients (30%) entered remission of T2DM, but remission of T2DM could not halt the DR progression. CONCLUSION: Diabetic retinopathy progression can occur in patients with or without before DR after bariatric surgery, regardless of remission of T2DM. All patients with T2DM should be examined regularly by an ophthalmologist postoperatively, and more carefully patients with previous DR or albuminuria.

Eliminating the heart from the curcumin molecule: monocarbonyl curcumin mimics (MACs).

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin's Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin's assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10-20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer's disease and malaria.

Noninfectious Uveitis Risk After COVID-19 Vaccination: A Nationwide Retrospective Cohort Study.

PURPOSE: To investigate the incidence and risk of noninfectious uveitis (NIU) following COVID-19 vaccination compared with an unvaccinated, uninfected control group. DESIGN: Retrospective population-based cohort study. METHODS: We included 5,185,153 individuals who received the first vaccine dose in the exposed group and 2,680,164 individuals in the unexposed, uninfected control group. The study observed for 180 days from their index date. Cumulative incidence and risk of NIU following COVID-19 vaccination, and attributable risk factors were assessed. RESULTS: Multivariable analysis showed elevated risk of nonanterior NIU within 60 days (hazard ratio [HR] 1.27 [95% confidence interval {CI} 1.03-1.55] and 61-180 days (HR 1.39 [95% CI 1.20-1.62]). Subgroup analysis highlighted an increased risk in females for early and delayed nonanterior uveitis (HR 1.44 [95% CI 1.08-1.92]; HR 1.78 [95% CI 1.43-2.20], respectively). Regardless of the location and onset timing of uveitis, a history of NIU was identified as the most significant risk factor, with a high hazard ratio ranging from 100 to 200. CONCLUSIONS: COVID-19 vaccination may modestly increase the risk of nonanterior uveitis especially in females. Despite adjustments, bias may persist in the exposed group, owing to significant differences between unexposed and exposed groups and low incidence of nonanterior uveitis in the unexposed group. Future research should aim to refine these findings by assessing uveitis risk in prior NIU patients and by enlarging the sample size or cohort matching.

Real-World Incidence of Incident Noninfectious Uveitis in Patients Treated With BRAF Inhibitors: A Nationwide Clinical Cohort Study.

PURPOSE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy. DESIGN: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration. RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis. CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.

Uveitis Risk After the First Dose of COVID-19 Vaccination Based on Uveitis History: Matched Cohort and Crossover Case Series Study.

PURPOSE: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history. DESIGN: Retrospective matched cohort and crossover case series study. METHODS: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis. RESULTS: In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively. CONCLUSIONS: COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history.

Incidence and Risk of Depressive Disorder in Patients With Retinitis Pigmentosa.

Importance: There is a lack of large-scale clinical studies exploring mental health among patients with retinitis pigmentosa (RP). Additionally, few studies have evaluated the associations of visual impairment with mental health in young patients. Objective: To investigate the association between depressive disorder and RP. Design, Setting, and Participants: This was a retrospective, nationwide, population-based cohort study using data obtained from the Health Insurance Review and Assessment service in Korea between 2008 and 2022. A total of 10 879 individuals who were newly diagnosed with RP between January 2011 and December 2021, as verified by both the RP registration code (National Registry of Rare and Intractable Disease in Korea code V209) and diagnostic code (International Statistical Classification of Diseases, 10th Revision code H35.51), were included. Data analysis was performed from October 2023 to January 2024. Exposure: Diagnosis of RP. Main Outcomes and Measures: Participants were categorized into 3 groups based on age at diagnosis (<20, 20-39, and ≥40 years). The incidence of depressive disorder in RP was determined after excluding those diagnosed with depressive disorder prior to RP diagnosis. Age- and sex-adjusted standardized incidence ratios (SIRs) of depressive disorder in patients with RP compared with the general population were calculated. Subgroup analyses by sex and age group were conducted. Results: A total of 10 879 patients (638 aged <20 years, 2233 aged 20-39 years, and 8008 aged ≥40 years; 5710 [52.5%] female) newly diagnosed with RP between 2011 and 2021 were included. The 10-year cumulative incidence of depressive disorder was 17.67% (95% CI, 16.57%-18.84%) in patients with RP. Subgroup analysis showed higher incidence of depressive disorder in female patients (hazard ratio [HR], 1.46; 95% CI, 1.29-1.65; P < .001) and those aged 40 years or older (HR, 1.93; 95% CI, 1.63-2.29; P < .001). The overall SIR of depressive disorder in patients with RP was 1.19 (95% CI, 1.12-1.27; P < .001), indicating a higher risk of depressive disorder compared with that in the general population. Both male and female patients with RP showed increased incidence rates of depressive disorder (17.53 [95% CI, 15.91-19.27] and 25.57 [95% CI, 23.58-27.67] per 1000 person-years, respectively) and increased SIRs of depressive disorder (1.21 [95% CI, 1.10-1.33] and 1.18 [95% CI, 1.09-1.28], respectively) (all P < .001) compared with the general population. Subgroup analysis by age group showed that the SIR peaked in patients in their 20s (1.50; 95% CI, 1.17-1.90; P = .006) and aged 60 years or older (1.25; 95% CI, 1.14-1.37; P < .001). Conclusions and Relevance: Individuals diagnosed with RP had a higher risk of developing depressive disorder. These findings support consideration of providing emotional and social support to patients with RP.