Importance of Higher-Order Aberrations on Both Anterior and Posterior Surfaces After Pterygium Surgery.

PURPOSE: The purpose of this study was to investigate the changes in higher-order aberrations (HOAs), coma, and spherical aberrations (SAs) on the anterior, posterior, and total corneal surfaces after pterygium excision. METHODS: In this single-center study, we examined 19 eyes of 15 patients who underwent pterygium excision at Yokohama Minami Kyosai Hospital between January 2017 and December 2017. We also evaluated 25 eyes of 25 age-matched patients with no history of ocular disease as the control group. Corneal topography, total HOAs, coma, and SAs in all regions at 4 and 6 mm diameters were evaluated using anterior segment optical coherence tomography (CASIA SS-1000, Tomey, Japan). The pterygium area and extent were also assessed. RESULTS: Significant improvements in the HOAs, coma, and SAs at both diameters were observed in the total and anterior corneas from the first postoperative month. Notably, the posterior cornea showed significant improvements in HOAs (4 mm: P < 0.001 [log HOAs]; 6 mm: P = 0.001 [log HOAs]) and coma (4 mm: P = 0.003 [log coma], 6 mm: P = 0.002 [log coma]) within both diameters at 1 month postoperatively. A strong correlation was identified among the pterygium area, posterior HOAs, and coma (Spearman correlation = 0.651). Pterygium induced 2 D of astigmatism when extension exceeded 2.1 mm. CONCLUSIONS: HOAs in both the anterior and posterior corneas improved after pterygium excision. This finding underscores the importance of considering corneal aberrations on both anterior and posterior surfaces in pterygium management.

Double-Bubble Technique Assisted by Holding Forceps: A Modified Technique in Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes With Scleral Fixated Intraocular Lens.

PURPOSE: Several techniques have been developed for graft unfolding approaches in Descemet membrane endothelial keratoplasty (DMEK). However, despite these techniques, graft deployment and configuration in eyes with deep anterior chambers remain challenging in some cases. Therefore, in this study, we described a modified technique for DMEK, known as the "double-bubble technique assisted by holding forceps." METHODS: This was a retrospective interventional case series. Patients who underwent DMEK between August 2022 and July 2023, including cases with a history of vitrectomy and scleral fixation of intraocular lens, were enrolled in this study. Two experienced surgeons performed DMEK. In brief, after graft insertion into the anterior chamber, the first bubble with a small volume of air was injected above the graft to open the tight roll, and the graft edge was held using a 25-gauge graft manipulator. The second bubble was injected underneath the graft for fixation, while the graft edge was grasped using forceps during gas injection. The graft was released from the forceps. Best spectacle corrected visual acuity, central corneal thickness, endothelial cell density, and incidence of postoperative complications were measured before and after DMEK. RESULTS: Eleven eyes of 11 patients were included in this study (mean follow-up period, 4.5 ± 4.4 months). Best spectacle corrected visual acuity and central corneal thickness significantly improved postoperatively ( P < 0.001). Rebubbling was required in 2 eyes; no other postoperative complications or primary graft failure were observed. CONCLUSIONS: The present technique enables safe and feasible DMEK surgery in vitrectomized eyes with scleral fixated IOLs and in those with a deep anterior chamber.

Assessment of Mucin-Associated Gene Expression Levels on the Ocular Surface.

The ocular surface is covered with a mucus layer. The mucin-associated genes expressed in the ocular surface cells include MUC1, MUC4, MUC5AC, and MUC16. Impression cytology is useful for collecting specimens from the ocular surface, their histological examination, and measuring mucin-associated gene expression levels. The expression of mucin-associated gene levels was assessed by quantitative polymerase chain reaction. The expression levels of these mucin-associated genes are potential biomarkers for ocular surface diseases, including dry eye disease.

The Effect of Anti-Autotaxin Aptamers on the Development of Proliferative Vitreoretinopathy.

This study investigated the effect of anti-autotaxin (ATX) aptamers on the development of proliferative vitreoretinopathy (PVR) in both in vivo and in vitro PVR swine models. For the in vitro study, primary retinal pigment epithelial (RPE) cells were obtained from porcine eyes and cultured for cell proliferation and migration assays. For the in vivo study, a swine PVR model was established by inducing retinal detachment and injecting cultured RPE cells (2.0 × 106). Concurrently, 1 week after RPE cell injection, the anti-ATX aptamer, RBM-006 (10 mg/mL, 0.1 mL), was injected twice into the vitreous cavity. Post-injection effects of the anti-ATX aptamer on PVR development in the in vivo swine PVR model were investigated. For the in vitro evaluation, the cultured RPE cell proliferation and migration were significantly reduced at anti-ATX aptamer concentrations of 0.5-0.05 mg and at only 0.5 mg, respectively. Intravitreal administration of the anti-ATX aptamer also prevented tractional retinal detachment caused by PVR in the in vivo PVR model. We observed that the anti-ATX aptamer, RBM-006, inhibited PVR-related RPE cell proliferation and migration in vitro and inhibited the progression of PVR in the in vivo model, suggesting that the anti-ATX aptamer may be effective in preventing PVR.

Descemet Membrane Endothelial Keratoplasty in Corneal Endothelial Decompensation After a Forceps-Induced Corneal Birth Injury: Case Series and Technique.

PURPOSE: The aim of this study was to describe the efficacy of Descemet membrane endothelial keratoplasty (DMEK) in patients with corneal endothelial decompensation secondary to a forceps-induced corneal birth injury. METHODS: This was a retrospective, noncomparative, interventional case series. Four eyes of 4 patients (1 female and 3 males; mean age, 64.0 ± 4.7 years) with corneal endothelial decompensation due to forceps-induced corneal birth injury were included. DMEK was performed in all cases, using a combined technique, including the use of intraoperative optical coherence tomography, vital staining of Descemet membrane of both host and donor, removal of scarred Descemet membrane with side-port forceps and vitreous cutter to smoothen the posterior corneal surface, epithelial peeling, and illumination for visualization. The examination included preoperative and postoperative ophthalmologic examinations: best-corrected visual acuity (converted to logarithm of the minimum angle of resolution [logMAR]), intraocular pressure, endothelial cell density (ECD), and central corneal thickness. RESULTS: No postoperative complications were noted, and corneal transparency was maintained during follow-up (mean follow-up period, 32.0 ± 27.0 months; range, 3-71 months). The mean best-corrected visual acuity was 0.52 ± 0.35 logMAR preoperatively and 0.15 ± 0.09 logMAR at the last visit. The mean postoperative ECD was 1632 ± 631 cells/mm2 (mean ECD at baseline, 3167 cells/mm2). Central corneal thickness decreased from 640 ± 67 µm preoperatively to 576 ± 58 µm postoperatively. CONCLUSIONS: This study suggests that DMEK can be performed uneventfully in eyes with a forceps-induced corneal birth injury. The combination of surgical techniques may be an effective approach for DMEK.

Incidence of Graft Rejection in Descemet Membrane Endothelial Keratoplasty After COVID-19 mRNA Vaccination.

PURPOSE: The aim of this study was to investigate the Descemet membrane endothelial keratoplasty (DMEK) rejection rate after COVID-19 vaccination with an mRNA vaccine. METHODS: This was a multicenter, retrospective cohort study. A total of 198 patients who underwent DMEK between January 2006 and December 2020 were divided into 2 cohorts: consecutive patients who received at least 1 COVID-19 vaccination in 2021 (vaccination started from February 2021 in Japan) and nonvaccinated patients (control cohort). Patients who had a postoperative observation period of less than 90 days were excluded. The main outcome measurement was the incidence of graft rejection. A Cox proportional hazards regression model was used for comparisons with the nonvaccinated group. RESULTS: Six rejection episodes were observed in 198 patients (124 nonvaccinated and 74 vaccinated patients), with 1 occurring in the nonvaccinated group and 5 in the vaccinated group. In the univariate model, vaccination had a significant effect on rejection episodes ( P = 0.003). The effect of vaccination was also significant ( P = 0.004) after adjusting for covariates. CONCLUSIONS: This study suggests that there may be a higher rejection rate after COVID-19 vaccination in patients who underwent DMEK. Patients should be warned of the rejection risk and its typical symptoms before receiving an mRNA COVID-19 vaccine, although further larger studies are needed to confirm the involvement of vaccination.

A case of acute syphilitic posterior placoid chorioretinitis showing improved choroidal blood flow after treatment.

Purpose: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare form of ocular syphilis. However, its pathophysiology is not fully understood. Laser speckle flowgraphy (LSFG) can facilitate the non-invasive evaluation of blood flow and allow investigations into the effects of treatments in various ocular diseases. We report a case of ASPPC that presented with symptoms only in the right eye but showed bilateral disease in LSFG. Observations: A 54-year-old man presented with decreased vision and visual field defects in the right eye 2 days prior to the initial visit. Fundoscopy images showed a typical yellowish placoid lesion in the macular area, and optical coherence tomography showed disruption of the outer retinal layers and nodular appearance of the retinal pigment epithelium. Fluorescence angiography showed excessive leakage of the placoid lesion characterized by hypofluorescent dots in the inner area ("leopard spotting"). The patient was diagnosed with unilateral ASPPC based on multiple imaging and serological tests. Penicillin was administered for 2 weeks, and the patient showed improvement in symptoms and restoration of the retinal structure. The mean blur rate of the right/left eye was 2.1/5.9 arbitrary units (AU) before treatment and increased to 4.5/9.3 AU 6 months after treatment. Conclusions and importance: Despite the absence of typical imaging signs and symptoms in the left eye, both eyes may have been affected with different degrees of severity. Thus, LSFG may facilitate the evaluation of treatment effects and the prediction of ocular inflammatory diseases in the early stages.

A Case of Bilateral Frosted Branch Angiitis after mRNA COVID-19 Vaccination.

We report a case of bilateral frosted branch angiitis (FBA) following mRNA-1273 COVID-19 vaccination. A 79-year-old male was referred to our hospital with a sudden onset of blurred vision in the right eye, which occurred during his return home after receiving the third dose of a messenger RNA (mRNA) COVID-19 vaccine. Fundoscopy revealed severe retinal vasculitis with sheathing of the artery and vein in the right eye more so than in the left eye, suggestive of bilateral FBA. Optical coherence tomography showed significant macular edema and serous retinal detachment in the right eye. Polymerase chain reaction assay detected Epstein-Barr virus (EBV) in the aqueous humor, and antibody against the EBV viral capsid antigen was positive for IgM. The next day, best-corrected visual acuity (BCVA) worsened to 0.08 due to macular edema in the left eye. After 2 courses of pulse steroid therapy and intravenous infusion of acyclovir, macular edema had disappeared and sheathing of retinal vessels was improving. At 5 months after the mRNA COVID-19 vaccination, BCVA was maintained 0.15 in the right eye and 0.7 in the left eye. Severe uveitis, such as FBA, can occur after mRNA COVID-19 vaccination.

Dilation of porcine retinal arterioles to nobiletin, a polymethoxyflavonoid: Roles of nitric oxide and voltage-dependent potassium channel.

We examined the effects of nobiletin, a polymethoxyflavonoid, on the retinal microvascular diameter to determine if they depend on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded diametric responses to nobiletin. The retinal arterioles dilated in a nobiletin concentration-dependent (100 pM-10 µM) manner and decreased by 50% after endothelial removal. The nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), reduced nobiletin-induced vasodilation comparable to denudation. Blockade of soluble guanylyl cyclase by 1H-[1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) produced a similar inhibitory effect as that by L-NAME. Nobiletin-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium (TEA), and the voltage-gated K (Kv) inhibitor, 4-aminopyridine. Co-administration of L-NAME and TEA almost eliminated nobiletin-induced vasodilation. Nobiletin elicits both endothelium-dependent and -independent dilation of retinal arterioles mediated by NO release and Kv channel activation, respectively.

Investigation of the Sectorized Corneal Thickness of Eyes With Corneal Endothelial Dysfunction Using Anterior-Segment Optical Coherence Tomography.

PURPOSE: The aim of this study was to investigate the sectorized corneal thickness of eyes with corneal endothelial dysfunction using anterior-segment optical coherence tomography. METHODS: We retrospectively collected anterior-segment optical coherence tomography data conducted before endothelial keratoplasty on 53 eyes of 53 patients with corneal endothelial dysfunctions including Fuchs endothelial corneal dystrophy, bullous keratopathy (BK) after trabeculectomy, and BK after laser iridotomy and from 18 normal eyes of 18 subjects. The imaging points were divided into 17 sectors. The mean for each sector was calculated and compared with the corresponding superior/inferior and temporal/nasal sectors. RESULTS: In the normal eyes, the superior sectors were thicker than the inferior and the temporal sectors thinner than the nasal. In the diseased eyes, the superior sectors were thicker than the inferior in all subgroups; however, this tendency was no longer observed after the values were divided by the mean for the normal eyes. No significant differences were found on horizontal comparisons; however, after the values were divided by the mean for the normal eyes, the temporal sectors were thicker than the nasal. When comparing the values between the with-hole and the without-hole sides in the BK after laser iridotomy eyes, the sectors on the with-hole side were thicker than the other side. CONCLUSIONS: Corneal thickness of endothelial dysfunction was thicker in the superior sectors than the inferior but at a similar level to normal eyes. No significant differences were found for horizontal comparisons but, based on comparison with the normal eyes, the temporal sectors were thicker than the nasal.

Rapid detection and diagnosis of herpetic keratitis using quantitative microfluidic polymerase chain reaction system for herpes simplex and varicella-zoster virus DNA: a case series.

BACKGROUND: A microfluidic real-time polymerase chain reaction (PCR) system can rapidly detect the viral DNA in specimens. Detection of herpes simplex virus (HSV) and varicella-zoster virus (VZV) DNA in tears is a useful diagnostic tool for herpes simplex virus keratitis (HSK) and herpes zoster ophthalmicus (HZO). METHODS: In total, 20 patients were included in this cross-sectional study. Among them, 8 patients with infectious epithelial HSK and 12 patients with HZO were included in HSK and HZO groups, respectively. In addition, 8 patients with non-herpetic keratitis and 4 healthy individuals without keratitis were included in the control group. Numbers of HSV and VZV DNA copies in tears of all patients and individuals were evaluated using a microfluidic real-time PCR system. Regarding HSV/VZV DNA test, tear specimens were collected by filter paper method using Schirmer's test paper, and subsequently, DNA was extracted from the filter paper using an automated nucleic acid extractor. Afterward, quantitative PCR was performed using a microfluidic real-time PCR system. RESULTS: From tear collection to real-time PCR result determination, the HSV/VZV DNA test took approximately 40 min. In the HSK group, the sensitivity and specificity of the HSV DNA tests were 100% each. The median value (range) of number of HSV DNA copies for affected eyes was 3.4 × 105 copies/µL (under a lower detection limit of 7.6). In the HZO group, the sensitivity and specificity of the VZV DNA tests were 100% each. The median value (range) of number of VZV DNA copies for affected eyes was 5.3 × 105 copies/µL (under a lower detection limit of 5.6 × 10-2). CONCLUSION: In conclusion, quantitative PCR for HSV and VZV DNA in tears using a microfluidic real-time PCR system is useful for diagnosing and monitoring HSK and HZO.

A Comparison of the Corneal Thickness Following Descemet's Stripping Automated Endothelial Keratoplasty and Descemet's Membrane Endothelial Keratoplasty.

PURPOSE: To compare the central corneal thickness before and after Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK), and to evaluate the recipient corneal thickness following DSAEK. METHODS: The corneal thickness was compared between two groups of eyes following DMEK and DSAEK, performed by a single surgeon between 2015 and 2017. We evaluated the recipient corneal thickness and central corneal thickness pre- and postoperatively at 1, 3, and 6 months using anterior segment optical coherence tomography. Recipient corneal thickness was defined as the corneal thickness without graft thickness. RESULTS: We included DMEK and DSAEK eyes (n = 26 each), which were similar in terms of their etiologies. Preoperatively, there was no significant difference in the central corneal thickness between the groups (DSAEK, median [interquartile range]: 721 [606.5 to 847.8] µm; and DMEK: 690 [618 to 722.3] µm; p = 0.30). Despite the tendency of the central corneal thickness to be significantly greater (p < .01) at 6 months following DSAEK (619.5 [607.8 to 661.3] µm) compared with that following DMEK (497.5 [475.8 to 525.3] µm), there was no significant difference at 6 months between the recipient corneal thickness following DSAEK (488.5 [443.8 to 515] µm) and central corneal thickness following DMEK (p = 0.54). CONCLUSIONS: DSAEK eyes display a similar tendency of stromal thinning as DMEK eyes.

A novel instrument to determine hue discrimination.

PURPOSE: We report and verify a novel hue discrimination instrument. We also investigate its efficiency to determine hue discrimination in persons with normal color vision. STUDY DESIGN: Experimental and clinical investigation. METHOD AND STUDY PARTICIPANTS: The instrument setup comprises an optical unit and examination unit. The optical unit is composed of the same 2 spectrometers and their controllers, which enables the independent emission of different spectral lights. Two independent bundle fibers connect the optical unit and the examination unit. Two different wavelength lights are illuminated on the bipartite upper and lower circular objectives with a visual angle of 2 degrees in the examination unit. The examinee recognizes the difference in the spectral lights between the bipartite targets. Persons with normal color vision are examined and the findings are confirmed using the Ishihara Test for Colour Deficiency. RESULTS: The instrument could generate spectral light from 450 to 650 nm within 2-nm accuracy. The spectral light showed a different light intensity according to the spectral centroid, ranging from 450 to 650 nm, but the difference could be adjusted and was negligible in terms of determination of hue discrimination using the power meter. Three width slits, 0.2 mm, 0.5 mm, and 1.0 mm, to homogenize the light path were investigated. The half-width wavelength was accurate on each spectral centroid; however, the 0.5 mm slit was suitable to generate an efficient light path. The hue discrimination differed among the study participants. In general, at short and long wavelength lights, the hue discrimination range was large: about 15 nm at 450 nm and about 10 nm at 650 nm. Between 470 and 620 nm, the hue discrimination showed good sensitivity and specificity between 8 and 2 nm depending on the targeting wavelength lights. Intraindividual variation was small, ranging from 3 to 1 nm, thus indicating good repeatability. The time to examine the hue discrimination was about 20 min. CONCLUSION: This newly invented instrument using two independent spectrometer units enabled the determination of hue discrimination. The instrument's sensitivity and specificity including its repeatability were confirmed and indicated that the instrument could be a clinically applicable method.

Graft rejection episodes after keratoplasty in Japanese eyes.

We aimed to investigate the clinical characteristics and risk factors for graft rejection after keratoplasty in Japanese patients. We enrolled 730 cases (566 patients) of penetrating keratoplasty (PK, N = 198), Descemet's stripping automated endothelial keratoplasty (DSAEK, N = 277), non-Descemet's stripping automated endothelial keratoplasty (nDSAEK, N = 138), and Descemet membrane endothelial keratoplasty (DMEK, N = 117). The incidence, clinical characteristics, and possible risk factors for graft rejection were analyzed. Graft rejection occurred in 65 cases (56 patients, 8.9%). The incidence rate of rejection was highest with PK (3.45/100 person-years), followed by DSAEK (2.34), nDSAEK (1.55), and DMEK (0.24). Cox regression analysis revealed keratoplasty type, younger age, indications (such as failed keratoplasty and infection), and steroid eyedrop use as possible risk factors. In the multivariate model adjusting baseline characteristics, PK and DSAEK had significantly higher hazard ratios (HRs) than DMEK (HR = 13.6, 95% confidence interval [CI] [1.83, 101] for PK, 7.77 [1.03, 58.6] for DSAEK). Although not statistically significant, the HR estimate of nDSAEK to DMEK (HR = 7.64, 95% CI [0.98, 59.6]) indicated higher HR in nDSAEK than in DMEK. DMEK is the favorable option among the four surgical procedures to avoid graft rejection after keratoplasty.

A pilot study of diabetic retinopathy in a porcine model of maturity onset diabetes of the young type 3 (MODY3).

Diabetic retinopathy (DR) is a leading cause of blindness in the working population. Because novel therapeutic intervention require testing, there is an urgent need for reliable animal models that faithfully replicate DR. Pig eyes have many similarities to human eyes anatomically and physiologically. Thus, attempts have been made to establish porcine models of DR by surgical, pharmaceutical or genetical induction of insulin deficiency, and dietary intervention. A previous study reported a transgenic pig model of maturity onset diabetes of the young type 3 (MODY3) developed signs of severe DR such as hemorrhage and proliferative tissue at the surface of the retina. However, the course of development of DR has not been studied in detail in this model. The purpose of this study was to investigate the early phase of DR in a MODY3. MODY3 and wild-type (WT) pigs underwent fundus photography and fluorescein angiogram (FA) before they developed cataracts. Animals were euthanized at age 1, 4, 7, and 10 months. Whole-mount retina and 10-µm thick paraffinized sections were stained with isolectin B4, and vessel density was determined by MATLAB software. At 4 and 7 months, retinal arterioles were immediately cannulated, and vasomotor action was measured by incubation with bradykinin and sodium nitroprusside. In the MODY3 pigs, fasting blood sugar levels gradually increased up to 500 mg/dL. Vascular tortuosity and yellowish spindle-shaped lesions were confirmed in MODY3 pigs at the age of 7 months; however, no microaneurysms were detected on FA. Compared with age-matched WT pigs, MODY3 pigs showed a significant decrease in blood vessel density in the intermediate and deep vascular plexus at 4 and 7 months of age and a slight decrease in capillary density in the superficial vascular plexus at 7 months of age. In MODY3 pigs, electron microscopy revealed thickening of the capillary basement membrane and leukostasis in the major blood vessels at 10 months of age. Bradykinin-induced dilation of retinal arterioles was diminished in MODY3 pigs as early as 7 months of age. Within 1 year after birth, MODY3 pigs show all typical early vascular lesions of diabetes except for microaneurysm formation. This pilot study suggests that the MODY3 pigs may serve as a suitable DR model to test effects of newly developed compounds on DR.

Risk factors for intraocular pressure elevation following Descemet membrane endothelial keratoplasty in Asian patients.

PURPOSE: To investigate risk factors for increased intraocular pressure (IOP) after Descemet membrane endothelial keratoplasty (DMEK) in Asian patients. METHODS: Data from January 2015 to February 2021 were obtained from our prospective database. IOP elevation after DMEK was defined as IOP ≥ 22 mmHg or an increase in IOP of ≥ 10 mmHg from baseline. In addition, we examined maximum IOP. Using iCare, we measured IOP 1, 2, 3, and 6 months after DMEK, and every 6 months thereafter. Logistic regression and linear regression were performed to find factors predictive of IOP elevation and maximum IOP, respectively, based on the results of univariate analysis. RESULTS: We enrolled 90 eyes (mean patient age, 74.9 ± 7.5 years; mean follow-up duration, 25.6 ± 9.9 months) that underwent DMEK. IOP elevation was present in 19 eyes (21%). IOP increased from 12.6 ± 3.9 mmHg preoperatively to a postoperative maximum of 17.0 ± 5.5 mmHg up to 36 months after DMEK (p < 0.0001). In univariate logistic regression analysis for IOP elevation, only one variable, pseudoexfoliation syndrome (PEX) and preexisting glaucoma, was significant (p < 0.05). Preexisting glaucoma without PEX (OR, 19.33; 95% CI, 4.75-93.46), PEX without glaucoma (OR, 7.25; 95% CI, 1.20-41.63), and PEX glaucoma (OR, 58.00; 95% CI, 6.78-1298.29) were associated with higher risk of IOP elevation. CONCLUSIONS: In this cohort, the eyes of patients with PEX and preexisting glaucoma were found to be prone to IOP elevation after DMEK.

Modulation of Hypoxia-Inducible Factors and Vascular Endothelial Growth Factor Expressions by Superfood Camu-Camu (Myrciaria dubia) Treatment in ARPE-19 and Fetal Human RPE Cells.

Background: Anti-vascular endothelial growth factor (anti-VEGF) therapy via intravitreal injection is an effective treatment for patients with abnormal ocular neovascularization, such as age-related macular degeneration (AMD) and diabetic macular edema (DME). However, prolonged and frequent anti-VEGF treatment is associated with a risk of local and systemic adverse events, including geographic atrophy, cerebrovascular disease, and death. Furthermore, some patients do not adequately respond to anti-VEGF therapy. Hypoxia-inducible factor (HIF) is a transcription factor that controls the expression of hypoxia-responsive genes involved in angiogenesis, inflammation, and metabolism. The HIF/VEGF pathway plays an important role in neovascularization, and the inhibition of HIF activation could be an effective biomolecular target for neovascular diseases. The demand for disease prevention or treatment using functional foods such as superfoods has increased in recent years. Few reports to date have focused on the antineovascular effects of superfoods in the retinal pigment epithelium (RPE). In light of the growing demand for functional foods, we aimed to find novel HIF inhibitors from superfoods worked in RPE cells, which could be an adjuvant for anti-VEGF therapy. Methods: Seven superfoods were examined to identify novel HIF inhibitor candidates using luciferase assay screening. We used the human RPE cell line ARPE-19 and fetal human RPE (fhRPE) to investigate the biomolecular actions of novel HIF inhibitors using quantitative PCR and western blotting. Results: Under CoCl2-induced pseudohypoxic condition and 1% oxygen hypoxic incubation, camu-camu (Myrciaria dubia) showed HIF inhibitory effects determined by luciferase assays. Camu-camu downregulated HIF-1α and VEGFA mRNA expressions in a concentration-dependent manner. Camu-camu also inhibited HIF-1α protein expressions, and its inhibitory effect was greater than that of vitamin C, which is present at high levels in camu-camu. Conclusion: The camu-camu extract suppressed the activation of HIF and VEGF in RPE cells. This could assist anti-VEGF therapy in patients with abnormal ocular neovascularization.

Two cases of dupilumab-associated conjunctivitis with high expression of IL-8 mRNA on the ocular surface: a case report.

BACKGROUND: Dupilumab-induced ocular surface disease (DIOSD) has been reported in patients with atopic dermatitis treated with dupilumab, and has been recognized as an adverse event of dupilumab. Our objective was to describe two cases of DIOSD with alterations in eotaxin-2 and interleukin (IL)-8 messenger ribonucleic acid (mRNA) expression on the ocular surface. CASE PRESENTATION: In the ocular surface test, specimens were collected from the patient's ocular surface, and eotaxin-2 and IL-8 mRNA levels in the specimens were measured using real-time polymerase chain reaction. The clinical score of ocular surface findings was quantified using a 5-5-5 exacerbation grading scale for allergic conjunctivitis. The first case was of a 27-year-old man who developed DIOSD 3 months after starting treatment with dupilumab injection for atopic dermatitis. After 5 weeks of topical instillation of tacrolimus ophthalmic suspension, the clinical score of ocular surface findings improved and IL-8 and eotaxin-2 mRNA expression levels gradually decreased. The second patient was a 55-year-old man who developed DIOSD 11 weeks after the start of treatment with dupilumab injection for atopic dermatitis. Four weeks after starting ophthalmological treatment with tacrolimus ophthalmic suspension, his clinical scores on ocular surface findings improved and IL-8 mRNA expression levels decreased. The ocular surface test in this case revealed increased expression levels of IL-8 mRNA on the ocular surface at the onset of DIOSD, which decreased with the improvement of objective findings. CONCLUSIONS: DIOSD, which has been successfully treated with tacrolimus ophthalmic suspension, may involve IL-8-related inflammation in addition to type 2 inflammation.