Functions of mucosal associated invariant T cells in eye diseases.

Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye. The protective functions of MAIT cells are induced by T-cell receptor (TCR)-mediated activation. However, the underlying mechanisms remain unclear. Thus, this mini-review aims to discuss our findings and the complexity of MAIT cell-mediated immune regulation in the eye.

Genotypes and clinical features of RHO-associated retinitis pigmentosa in a Japanese population.

PURPOSE: To report the genotypes and clinical features of RHO-associated retinitis pigmentosa (RHO-RP) in the Kyushu region of Japan. STUDY DESIGN: Retrospective, single-center study. METHODS: Sixteen RP patients with pathogenic RHO variants seen at Kyushu University Hospital were investigated. Clinical data including age, best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) units, visual field, fundus photography, and optical coherence tomography were retrospectively obtained. Visual outcomes were compared between classical and sector phenotypes and among genetic variants. RESULTS: The mean age at the first visit was 54.0 ± 15.7 years, with a mean follow-up of 7.6 ± 4.0 years. Fourteen patients (87.5%) showed the classical RP phenotype, of whom four were associated with p.[Pro23Leu] and two had p.[Pro347Leu] variants. In addition, two patients with the sector phenotype harbored p.[Ala164Val] variants. Among the classical RHO-RP patients, the mean BCVA decreased from 0.60 to 1.08 logMAR over the follow-up period (7.4 ± 4.1 years) whereas BCVA was preserved at 0.04 logMAR in sector RHO-RP patients (9.0 ± 3.0 years). Genotype-to-phenotype analysis demonstrated that p.[Pro347Leu] was associated with severe vision loss at an earlier age. Macular complications such as epiretinal membrane and cystoid macular edema were observed in 5 classical RHO-RP patients. CONCLUSION: p.[Pro23Leu], but not p.[Pro23His], was a frequent variant causing RHO-RP in the Kyushu region of Japan. As reported in previous studies, patients with the p.[Pro347Leu] variant showed a more severe phenotype, and variants causing sector RHO-RP were associated with a good prognosis.

Clinical Features of Pediatric Uveitis at a Tertiary Referral Center in the Western Region of Japan.

PURPOSE: This study aimed to assess the clinical features of pediatric uveitis at a tertiary referral center in Western Japan. METHODS: One hundred forty eyes of 80 patients aged <20 years at the time of uveitis onset, who visited Kyushu University Hospital between January 2010 and December 2019 were included in this study. Clinical records were retrospectively reviewed. Demographics, clinical findings, treatments, and visual prognoses were compared between the disease groups. RESULTS: Of 80 patients, 32 were males and 48 were females. The average age of onset was 12.5 ± 4.8 (0-19) years. Tubulointerstitial nephritis and uveitis (TINU) and juvenile idiopathic arthritis (JIA) were the most frequent causes, accounting for 11.3% and 10% of cases, respectively, followed by sarcoidosis (5%), Behçet's disease, acute anterior uveitis, Vogt-Koyanagi-Harada disease, and juvenile chronic iridocyclitis (3.8% each). Infectious uveitis accounted for 7.6% of the cases: cytomegalovirus was the most frequent agent. Of these cases, 43.8% were unclassified. Systemic therapies were administered to 87.5% of the patients with JIA, 33.3% of those with TINU, and 28.6% of the other diagnostic groups. In the unclassified group, 80% of the patients were followed up with only topical corticosteroids. LogMAR visual acuity of 0 or less accounted for more than 80% in the final examination. CONCLUSION: TINU and JIA were the most common causes of pediatric uveitis. Although each required systemic therapy, most unclassified cases of pediatric uveitis were managed by topical corticosteroids alone with good visual prognosis. Accurate diagnosis is important for pediatric uveitis management.

Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis.

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

Persistence of vascular empty sleeves in choroidal neovascularization after VEGF therapy in both animal models and humans.

PURPOSE: Choroidal neovascularization (CNV) often recurs during anti-vascular endothelial growth factor (VEGF) therapy; however, little is known about the mechanism of vascular regrowth. Vascular regrowth along the empty sleeves of basement membranes was proposed as a mechanism for recurrence after the reversal of VEGF inhibition in tumors. This study investigated whether the proposed mechanism is involved in CNV during VEGF therapy. METHODS: We made two observations using a mice model, as well as patients with CNV. Laser-induced CNV mice were used to examine the vascular empty sleeves of the basement membrane and CNV with the immunohistochemistry of type IV collagen and CD31, respectively. A retrospective cohort study included 17 eyes from 17 patients with CNV treated with anti-VEGF treatment. Vascular regrowth during anti-VEGF treatment was assessed using optical coherence tomography angiography (OCTA). RESULTS: In the CNV mouse model, the CD31+ vascular endothelium area was decreased during anti-VEGF treatment compared with the IgG control (33516.7 ± 10864.7 vs. 10745.9 ± 5755.9 µm2, P < 0.05), whereas a significant difference was not observed in the area of type IV collagen+ vascular empty sleeve after the treatment compared with the control (29135.0 ± 7432.9 vs. 24592.0 ± 5935.3 µm2, P = 0.7). The proportions of CD31+ to type IV collagen+ areas were significantly decreased after the treatment (38.7 ± 7.4% vs. 17.1 ± 5.4%, P < 0.05). In the OCTA observations, the follow-up period in the retrospective cohort study was 58.2 ± 23.4 months. CNV regrowth was observed in 682 neovessels of the 17 eyes. In group 1, CNV regression and regrowth are in the same form (129 neovessels, 18.9%). In group 2, CNV regression and regrowth are in a different form (170 neovessels, 24.9%). In group 3, CNV regrowth is with a different form without the regression (383 neovessels, 56.2%). CONCLUSIONS: Parts of CNV regrowth may occur along the vascular empty sleeve, which remain after anti-VEGF treatment.

Long-term outcomes of infliximab in patients with Behçet's disease-associated uveitis.

OBJECTIVES: To evaluate long-term outcomes of infliximab (IFX) treatment in patients with Behçet's disease (BD)-associated uveitis. PATIENTS AND METHODS: We retrospectively analyzed the cases of patients with BD-associated uveitis treated with IFX for > 5 years. We compared the numbers of ocular inflammatory attacks, ocular disease activities, and visual acuity before and after the initiation of IFX treatment. RESULTS: The 24 patients were 20 men and 4 women. Their mean age at the initiation of IFX treatment was 37.3 ± 9.2 years. The mean term from the initiation of IFX treatment was 10.3 ± 2.4 years. The average number of ocular inflammatory attacks was 5.4 ± 2.1 per 12 months before the IFX treatment and significantly lower at 0.83 ± 0.96 per 12 months after the initiation of IFX treatment (p < 0.05). We used a scoring system for BD-associated uveitis named the Behçet's disease ocular attack score 24 (BOS24) to estimate the changes in ocular disease activities between before and after initiation of IFX treatment. The average score decreased significantly from 7.58 ± 2.77 to 2.55 ± 2.74 after the initiation of IFX treatment (p < 0.05). Even after > 5 years of the treatment, both the number of ocular attacks and the BOS24 score kept decreasing. The visual acuity in 42 of 48 eyes (24 patients) was improved or maintained. CONCLUSIONS: IFX was effective for controlling ocular inflammatory attacks and diminishing ocular disease activities in patients with BD-associated uveitis, and it maintained the patients' visual acuity.

Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which enables these CMV strains to escape HLA-E-restricted CD8+T cell responses. Variations in UL40 sequences have been studied mainly in the peripheral blood of CMV-viremia cases. In this study, we sought to investigate how ocular CMV disease develops from CMV infections. CMV gene sequences were compared between the intraocular fluids and peripheral blood of 77 clinical cases. UL40 signal peptide sequences were more diverse, and multiple sequences were typically present in CMV-viremia blood compared to intraocular fluid. Significantly stronger NK cell suppression was induced by UL40-derived peptides from intraocular HCMV compared to those identified only in peripheral blood. HCMV present in intraocular fluids were limited to those carrying a UL40 peptide sequence corresponding to the leader peptide sequence of the host's HLA class I, while UL40-derived peptides from HCMV found only in the peripheral blood were disparate from any HLA class I allotype. Overall, our analyses of CMV-retinitis inferred that specific HCMV strains with UL40 signal sequences matching the host's HLA signal peptide sequences were those that crossed the blood-ocular barrier to enter the intraocular space. UL40 peptide repertoires were the same in the intraocular fluids of all ocular CMV diseases, regardless of host immune status, implying that virus type is likely to be a common determinant in ocular CMV disease development. We thus propose a mechanism for ocular CMV disease development, in which particular HCMV types in the blood exploit peripheral and central HLA-E-mediated tolerance mechanisms and, thus, escape the antivirus responses of both innate and adaptive immunity.

Longer Interscan Times in OCT Angiography Detect Slower Capillary Flow in Diabetic Retinopathy.

Purpose: To investigate the detection of slower retinal capillary blood flow using commercial OCT angiography (OCTA) with a longer interscan time in diabetic retinopathy (DR). Design: Observational, prospective, cross-sectional study. Participants: A total of 62 eyes from 39 subjects with diabetes mellitus and 10 eyes from 9 healthy subjects. Methods: Commercial spectral domain-OCT was used to obtain 3 × 3-mm fovea-centered OCTA images of all eyes with 3 different interscan times (4.3, 5.7, and 8.6 ms). For each interscan time, OCTA imaging was performed 5 consecutive times, and a ×5 averaged image was obtained. Capillary flow density and visualization of retinal capillaries in the superficial and deep capillary plexuses (SCPs and DCPs, respectively) were compared between the 3 averaged images from the 3 different interscan times. Main Outcome Measures: Capillary flow density and visualization of foveal capillaries in 3 images with different interscan times. Results: Forty-five eyes of 34 patients were analyzed. There was no significant difference in the flow density of the SCP and DCP between the 3 images with different interscan times in all the DR stages. Some capillaries including microaneurysms that could not be observed at 4.3 ms could be observed at 5.7 or 8.6 ms. There were significantly more capillaries with difference points between the 3 images in the group with DR than in the group without DR (P < 0.01). The morphology of some microaneurysms also changed with longer interscan times. Conclusions: OCTA with longer interscan times revealed slower flow points in capillaries and more accurate visualization and morphology of microaneurysms in DR.

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

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

Hyperreflective Membrane at the Vitreoretinal Interface in Diabetic Macular Edema: A Finding in Ultra-High-Resolution Optical Coherence Tomography.

Purpose: Detecting subtle vitreoretinal interface (VRI) findings, such as a posterior hyaloid membrane, is difficult with conventional retinal imaging. We compared ultra-high-resolution spectral domain optical coherence tomography (UHR-SD-OCT) with standard-resolution OCT (SD-OCT) for the imaging of VRI abnormalities in diabetic retinopathy (DR). Methods: This prospective cross-sectional study included 113 consecutive patients (91 patients with diabetes and 22 healthy controls). The VRI was evaluated, and the results were compared between the conventional SD-OCT and UHR-SD-OCT images. VRI findings were also investigated before and after internal limiting membrane peeling during vitrectomy for proliferative DR. Results: A total of 159 eyes (87.4%) of 91 patients with diabetes were analyzed. UHR-SD-OCT could detect a hyperreflective layer at the VRI, in which en face OCT showed a membrane-like structure, termed the hyperreflective membrane (HRMe). The preoperative HRMe could not be detected in all patients with proliferative DR who underwent internal limiting membrane peeling during vitrectomy. Although the HRMe did not correlate with the DR stage, eyes with diabetic macular edema (DME) (64.5%) showed a significant HRMe with UHR-SD-OCT more frequently than those without DME (35.8%) (P = 0.005). Conclusions: UHR-SD-OCT can detect the HRMe at the VRI in DR eyes, particularly in eyes with DME. The HRMe may present a thickened posterior hyaloid membrane that contributes to DME development. Translational Relevance: UHR-SD-OCT detects slight changes in the VRI in DR eyes. In the future, it may help to elucidate the mechanism of DME formation.

Panuveitis induced by donor-derived CD8+ T cells after allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia.

Purpose: This article presents a case of panuveitis that occurred after unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a patient with lymphoma-type human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL). Observations: A 45-year-old man developed unilateral panuveitis 18 months after undergoing allo-HSCT. He underwent vitrectomy, and depositions of grey-white granules localized on the retinal artery were observed in the eye. Cytological examination of the vitreous aspirates showed that the atypical lymphoid cells stained positive for CD3 and CD8, but negative for CD4, B-cell markers, and cytomegalovirus antigen. Interphase fluorescence in situ hybridization using X- and Y-chromosome probes revealed complete donor chimerism in CD8+ T cells in the vitreous aspirates. Conclusions and importance: Donor-derived CD8+ T lymphocytes can induce panuveitis like HTLV-1-assiciated uveitis after allo-HSCT in patients with ATL. Pathological diagnosis of vitreous infiltration by vitrectomy is helpful in patients with ATL. Donor-derived CD8+ T lymphocytes-induced panuveitis is recurrent but susceptible to regional corticosteroid treatment.

Morphology and fluorescein leakage in diabetic retinal microaneurysms: a study using multiple en face OCT angiography image averaging.

PURPOSE: To investigate the relevance of microaneurysm morphology in optical coherence tomography angiography (OCTA) image averaging and fluorescein leakage in diabetic retinopathy (DR). METHODS: In 38 consecutive patients with DR, ten consecutive 3- × 3-mm fovea-centered OCTA (HS100, Canon Inc., Tokyo, Japan) and fluorescein angiography (FA) were performed, and averaged OCTA images were created based on the 10 images. After detecting all microaneurysms in FA images, the morphology was classified into four types (focal bulge, saccular/pedunculated, fusiform, and mixed) using averaged OCTA images. The correlation between microaneurysm leakage in FA, retinopathy stage, and microaneurysm morphology was estimated. RESULTS: Thirty-eight eyes (50.0%) of the 33 patients were available for analysis, and 370 (63.5%) of the 583 FA-detected microaneurysms were morphologically classifiable (focal bulge, 46; saccular/pedunculated, 143; fusiform, 29; and mixed, 152) in OCTA. There was a significant correlation between stage and percentage of microaneurysm morphology and between morphology and the presence of leakage (P < 0.0001 and P < 0.01, respectively). The proportion of focal bulges decreased with stage progression, while the other three types increased with stage progression. The percentage of FA leakage for focal bulge, saccular/pedunculated, fusiform, and mixed was 41.3%, 66.4%, 82.8%, and 66.4%, respectively, and the fusiform type showed significant FA leakage. CONCLUSION: Microaneurysm morphology is correlated with the DR stage and FA leakage. Microaneurysm morphology recognition using OCTA image averaging may be useful for the clinical evaluation of DR.

Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa.

Retinitis pigmentosa (RP) is an intractable inherited disease that primarily affects the rods through gene mutations followed by secondary cone degeneration. This cone-related dysfunction can lead to impairment of daily life activities, and ultimately blindness in patients with RP. Paradoxically, microglial neuroinflammation contributes to both protection against and progression of RP, but it is unclear which population(s) - tissue-resident microglia and/or peripheral monocyte-derived macrophages (mφ) - are implicated in the progression of the disease. Here we show that circulating blood inflammatory monocytes (IMo) are key effector cells that mediate cone cell death in RP. Attenuation of IMo and peripherally engrafted mφ by Ccl2 deficiency or immune modulation via intravenous nano-particle treatment suppressed cone cell death in rd10 mice, an animal model of RP. In contrast, the depletion of resident microglia by a colony-stimulating factor 1 receptor inhibitor exacerbated cone cell death in the same model. In human patients with RP, IMo was increased and correlated with disease progression. These results suggest that peripheral IMo is a potential target to delay cone cell death and prevent blindness in RP.

Postoperative follow-up of submacular hemorrhage displacement treated with vitrectomy and subretinal injection of tissue plasminogen activator: ultrawide-field fundus autofluorescence imaging in gas-filled eyes.

PURPOSE: To investigate the utility of Optos ultrawide-field fundus autofluorescence (UWF-FAF) imaging for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal tissue-plasminogen activator (t-PA) injection for subretinal hemorrhage (SRH) displacement. STUDY DESIGN: Retrospective consecutive case series. METHODS: This study included 24 eyes with SRH. Vitrectomy with subretinal t-PA injection was performed, followed by postoperative prone positioning. FAF images acquired using Optos California were examined and the SRH occupancy in the macula was calculated. The main outcome measures were displacement rate and direction of SRH for 3 days postoperatively, and postoperative best-corrected visual acuity (BCVA). RESULTS: The postoperative BCVA ranged from improvement (23 eyes; 95.8%) to no change (one eye; 4.2%). Analysis was done using postoperative Optos FAF images for 20 eyes (83.3%). Postoperative SRH occupancy was significantly reduced, by 27.4%, compared with the preoperative occupancy (P = 0.03). A statistically significant reduction was found between the preoperative and postoperative day (POD)1 (P = 0.04), but not between POD1 and POD2 (P = 0.7), or between POD2 and POD3 (P = 1.0). CONCLUSION: UWF-FAF imaging is useful for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal t-PA injection for SRH displacement.

Increased vitreous levels of B cell activation factor (BAFF) and soluble interleukin-6 receptor in patients with macular edema due to uveitis related to Behçet's disease and sarcoidosis.

PURPOSE: Uveitis accounts for 10-15% of all cases of blindness in the developed world. Uveitic macular edema (UME) is a primary cause of permanent visual impairment in patients with uveitis. Because proinflammatory mediators elicit inflammation and lead to UME, we determined the profiles of proinflammatory mediators associated with complications, such as ME, in the vitreous humor of patients with panuveitis related to Behçet's disease (BD) and sarcoidosis. METHODS: In this retrospective study, we enrolled 21 patients with uveitis, including 6 with BD and 15 with sarcoidosis, and 15 patients with idiopathic epiretinal membrane (iERM) at the Department of Ophthalmology, Kyushu University Hospital, between January 2008 and April 2016. Vitreous concentrations of 32 proinflammatory mediators, including cytokines and soluble receptors of tumor necrosis factor (TNF) and interleukin (IL)-6 families, were assessed using a bead-based multiplex assay and their association with clinical data was examined. RESULTS: The levels of proinflammatory mediators, including a proliferation-inducing ligand (APRIL), B cell activating factor belonging to the TNF family (BAFF), soluble cluster of differentiation 30 (sCD30), soluble TNF receptor-1 (sTNFR1), sTNFR2, TNF-α, IL-6, and soluble IL-6 receptor-α (sIL-6Rα), were significantly higher in patients with uveitis. With regard to clinical parameters in patients with uveitis, vitreous levels of BAFF and sIL-6Rα were prominently elevated in patients with UME compared to in those without UME (P < 0.01, respectively). CONCLUSIONS: Our results suggest that elevated vitreous levels of BAFF and sIL-6Rα are associated with the pathogenesis of UME in patients with panuveitis related to BD and sarcoidosis.

Corrigendum: Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

[This corrects the article DOI: 10.3389/fimmu.2022.1008220.].

Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity.

Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt-Koyanagi-Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161highTRAV1-2+ mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of interleukin (Il) 22 and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of Il22, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.

Drainage Retinotomy Confers Risk of Epiretinal Membrane Formation After Vitrectomy for Rhegmatogenous Retinal Detachment Repair.

PURPOSE: To describe the factors associated with epiretinal membrane (ERM) formation in eyes treated with pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). DESIGN: Nationwide, multicenter, clinical cohort study based on registry data. METHODS: We reviewed 2239 cases treated with PPV for RRD repair registered in the Japan-Retinal Detachment Registry between February 2016 and March 2017. Associations of 13 baseline characteristics and 8 surgical procedures with ERM formation were evaluated using univariate analysis. We conducted a propensity score-matched analysis for the significantly associated clinical factor(s). The primary outcome measure was ERM formation after 6 months of vitrectomy. RESULTS: ERM had developed in 104 cases (4.6%) by 6 months. We found that drainage retinotomy was significantly associated with ERM after multiple testing correction (odds ratio [OR] 2.22 [95% confidence interval {CI} 1.50-3.31]; P < .001). In the propensity score-matched analysis (n = 492 in each group), we confirmed a significant difference in the incidence of ERM after 6 months of vitrectomy (8.3% and 2.6% in cases with and without drainage retinotomy, respectively; OR 3.35 [95% CI 1.77-6.33]; P < .001). CONCLUSIONS: Eyes treated with PPV combined with drainage retinotomy are more likely to develop ERM postoperatively.

RECURRENCE RATE OF CYSTOID MACULAR EDEMA WITH TOPICAL DORZOLAMIDE TREATMENT AND ITS RISK FACTORS IN RETINITIS PIGMENTOSA.

PURPOSE: To investigate the rate of the recurrence of cystoid macular edema (CME) secondary to retinitis pigmentosa (RP) after the initiation of topical dorzolamide and the recurrence risk factors. METHODS: We retrospectively analyzed the data of RP patients at Kyushu University Hospital. We included patients who showed a treatment response to 1.0% topical dorzolamide. The day of treatment initiation was set as the baseline. Topical dorzolamide treatment was continued during the follow-up. The recurrence of CME (defined as a >20% increase in central subfield thickness compared to previous visit, or a central subfield thickness value that exceed baseline value) was evaluated at each follow-up visit. Risk factors for RP-CME recurrence were analyzed by Cox proportional hazards modeling. A Kaplan-Meier survival analysis was used to evaluate the time to recurrent RP-CME. RESULTS: Forty RP-CME patients showed a treatment response to topical dorzolamide. During the mean 3.9-year follow-up, 14 patients exhibited recurrence; its rate was 15.6%, 34.7%, and 48.7% at 1, 3, and 5 years, respectively. A high baseline central subfield thickness was significantly associated with recurrent (hazard ratio 1.11, 95% CI: 1.05-1.18, P = 0.0004). CONCLUSION: The recurrence rate of RP-CME increased with time. A high baseline central subfield thickness value was a risk factor for recurrence.