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To describe the clinical presentation and treatment response of dupilumab-associated ocular surface disease (DAOSD).BACKGROUND/AIMSTo describe the clinical presentation and treatment response of dupilumab-associated ocular surface disease (DAOSD).This is a retrospective case series of atopic dermatitis patients with DAOSD treated with dupilumab. All consecutive patients with atopic dermatitis referred by dermatologists for suspicion of DAOSD between May 2018 and June 2020 were systemically assessed by a single ophthalmologist. Presenting signs of DAOSD, duration of treatment and associated response are described.METHODSThis is a retrospective case series of atopic dermatitis patients with DAOSD treated with dupilumab. All consecutive patients with atopic dermatitis referred by dermatologists for suspicion of DAOSD between May 2018 and June 2020 were systemically assessed by a single ophthalmologist. Presenting signs of DAOSD, duration of treatment and associated response are described.Twenty-eight patients had DAOSD during the study period. Average age was 45.6±14.8 years and 13 (46%) were female. Average follow-up was 15±10 months. Most presentations consisted in diffuse, inflammatory conjunctivitis (n=19, 68%). Other signs included peripheral corneal infiltrates (n=7, 25%), limbal nodules (n=7, 25%) and dry eye syndrome (n=6, 21%). To control ocular symptoms, tapering of corticosteroid eyedrops was slow: taper duration of strong and mild corticosteroid eyedrops averaged 10±8 weeks and 49±34 weeks, respectively. Four patients (14%) required an increase of corticosteroid eyedrops during taper due to clinical deterioration. Corticosteroid eyedrops were still required at final follow-up among 10 patients (36%). Dupilumab was temporarily stopped in 3 patients (11%), one of which did not wish to resume dupilumab for unrelated reasons. Symptomatic improvement and/or complete resolution was achieved in 25/26 patients at follow-up (96%) with empirical treatment.RESULTSTwenty-eight patients had DAOSD during the study period. Average age was 45.6±14.8 years and 13 (46%) were female. Average follow-up was 15±10 months. Most presentations consisted in diffuse, inflammatory conjunctivitis (n=19, 68%). Other signs included peripheral corneal infiltrates (n=7, 25%), limbal nodules (n=7, 25%) and dry eye syndrome (n=6, 21%). To control ocular symptoms, tapering of corticosteroid eyedrops was slow: taper duration of strong and mild corticosteroid eyedrops averaged 10±8 weeks and 49±34 weeks, respectively. Four patients (14%) required an increase of corticosteroid eyedrops during taper due to clinical deterioration. Corticosteroid eyedrops were still required at final follow-up among 10 patients (36%). Dupilumab was temporarily stopped in 3 patients (11%), one of which did not wish to resume dupilumab for unrelated reasons. Symptomatic improvement and/or complete resolution was achieved in 25/26 patients at follow-up (96%) with empirical treatment.DAOSD may follow the course of a chronic illness. Long-term corticosteroid eyedrops were required in many patients and when taper was possible, this was done after a prolonged treatment duration. Most patients' ocular symptoms could be controlled, allowing dupilumab continuation.CONCLUSIONSDAOSD may follow the course of a chronic illness. Long-term corticosteroid eyedrops were required in many patients and when taper was possible, this was done after a prolonged treatment duration. Most patients' ocular symptoms could be controlled, allowing dupilumab continuation.

Background/aimsTo improve the accuracy of pterygium screening and detection through smartphones, we established a fusion training model by blending a large number of slit-lamp image data with a small proportion of smartphone data.MethodTwo datasets were used, a slit-lamp image dataset containing 20 987 images and a smartphone-based image dataset containing 1094 images. The RFRC (Faster RCNN based on ResNet101) model for the detection model. The SRU-Net (U-Net based on SE-ResNeXt50) for the segmentation models. The open-cv algorithm measured the width, length and area of pterygium in the cornea.ResultsThe detection model (trained by slit-lamp images) obtained the mean accuracy of 95.24%. The fusion segmentation model (trained by smartphone and slit-lamp images) achieved a microaverage F1 score of 0.8981, sensitivity of 0.8709, specificity of 0.9668 and area under the curve (AUC) of 0.9295. Compared with the same group of patients’ smartphone and slit-lamp images, the fusion model performance in smartphone-based images (F1 score of 0.9313, sensitivity of 0.9360, specificity of 0.9613, AUC of 0.9426, accuracy of 92.38%) is close to the model (trained by slit-lamp images) in slit-lamp images (F1 score of 0.9448, sensitivity of 0.9165, specificity of 0.9689, AUC of 0.9569 and accuracy of 94.29%).ConclusionOur fusion model method got high pterygium detection and grading accuracy in insufficient smartphone data, and its performance is comparable to experienced ophthalmologists and works well in different smartphone brands.

AimTo develop an artificial intelligence (AI) algorithm that diagnoses cataracts/corneal diseases from multiple conditions using smartphone images.MethodsThis study included 6442 images that were captured using a slit-lamp microscope (6106 images) and smartphone (336 images). An AI algorithm was developed based on slit-lamp images to differentiate 36 major diseases (cataracts and corneal diseases) into 9 categories. To validate the AI model, smartphone images were used for the testing dataset. We evaluated AI performance that included sensitivity, specificity and receiver operating characteristic (ROC) curve for the diagnosis and triage of the diseases.ResultsThe AI algorithm achieved an area under the ROC curve of 0.998 (95% CI, 0.992 to 0.999) for normal eyes, 0.986 (95% CI, 0.978 to 0.997) for infectious keratitis, 0.960 (95% CI, 0.925 to 0.994) for immunological keratitis, 0.987 (95% CI, 0.978 to 0.996) for cornea scars, 0.997 (95% CI, 0.992 to 1.000) for ocular surface tumours, 0.993 (95% CI, 0.984 to 1.000) for corneal deposits, 1.000 (95% CI, 1.000 to 1.000) for acute angle-closure glaucoma, 0.992 (95% CI, 0.985 to 0.999) for cataracts and 0.993 (95% CI, 0.985 to 1.000) for bullous keratopathy. The triage of referral suggestion using the smartphone images exhibited high performance, in which the sensitivity and specificity were 1.00 (95% CI, 0.478 to 1.00) and 1.00 (95% CI, 0.976 to 1.000) for ‘urgent’, 0.867 (95% CI, 0.683 to 0.962) and 1.00 (95% CI, 0.971 to 1.000) for ‘semi-urgent’, 0.853 (95% CI, 0.689 to 0.950) and 0.983 (95% CI, 0.942 to 0.998) for ‘routine’ and 1.00 (95% CI, 0.958 to 1.00) and 0.896 (95% CI, 0.797 to 0.957) for ‘observation’, respectively.ConclusionsThe AI system achieved promising performance in the diagnosis of cataracts and corneal diseases.

Background/aimsThis retrospective multicentric panel study provides absolute numbers, types of and indications for corneal transplantation in Germany from 2011 to 2021 and sets them into the international context.MethodsA questionnaire was sent to the 104 German ophthalmologic surgery departments and 93 (89%) provided their data.ResultsThe number of reported keratoplasties more than doubled from 2011 (n=4474) to 2021 (n=8998). Lamellar keratoplasties (49% posterior (n=2883), 4% anterior (n=231)) surpassed penetrating keratoplasty (PKP, 47%, n=2721) for the first time in 2014. Since 2016, Descemet’s membrane endothelial keratoplasty (DMEK) has become the predominant keratoplasty procedure in Germany. Its number increased by 1.5-fold from 3850 (2016) to 5812 (2021). Main indications in 2021 were Fuchs’ endothelial corneal dystrophy (FECD, 43%), pseudophakic corneal decompensation (12%), repeated keratoplasty (11%), infections (7%), keratoconus (6%) and corneal scarring (4%, others: 9%). The PKP percentage decreased from 70.2% in 2011 (n=3141) to 31.7% in 2021 (n=2853). Descemet’s stripping (automated) endothelial keratoplasties (DSAEKs) decreased to 1% in 2021 (n=74). 98.6% of all posterior lamellar keratoplasties were DMEKs in Germany in 2021. The number of deep anterior lamellar keratoplasties (DALKs) remained comparable from 2011 (n=269) to 2021 (n=251, 2.8%).ConclusionMain indications for corneal transplantation in Germany (2021) were FECD and pseudophakic corneal decompensation. DMEK is by far the predominant corneal transplantation procedure since 2016 followed by PKP, whose absolute number decreased only slightly during the decade from 2011 to 2021. DALK proportions remain low, but stable, whereas DSAEK decreased annually and plays a minor role in Germany.Trial registration number NCT03381794.

AimTo interpret the likely clinical susceptibility of isolates from microbial keratitis (MK), we performed a meta-analysis of published data that measured the concentrations of topically applied antimicrobials in the cornea or aqueous humour. We then correlated these values with the in vitro minimum inhibitory concentration (MIC).MethodsWe searched PubMed to identify studies reporting aqueous and/or corneal concentrations of 53 topically applied ocular antimicrobials, spanning the following classes: beta-lactams, glycopeptides, aminoglycosides, chloramphenicol, lincosamides, macrolides, oxazolidinones, steroidal antimicrobials, tetracyclines, diaminopyrimidines, sulphonamides, lipopeptides and polymyxins. Two clinicians independently screened the abstracts and extracted data from studies meeting the inclusion criteria, including participant species, antimicrobial concentration, dosing regimens, epithelial status and measurement methods. Concentrations were standardised to mg/L. The data were stratified by applied concentration, dosing regime and species. First quartile concentrations (EQ1) were extrapolated to provide a conservative estimate and tabulated practice resource for clinicians treating MK.ResultsWe screened 7247 publications. 81 publications were included in the meta-analysis, comprising data on the aqueous and/or corneal concentrations of 28 antimicrobials. Bioassay was the most frequently used method for quantifying antimicrobial concentrations (25 studies), followed by liquid chromatography and fluorescence assays (18 studies each), mass spectrometry (12 studies) and radioactivity and colourimetric assays (3 studies each).ConclusionWe provide a practical resource for clinicians to assess whether the expected EQ1 of an antimicrobial in the cornea is above the in vitro MIC of the pathogen. This reduces reliance on systemic break-point concentrations. This enables standardised guidelines for evidence-based antimicrobial treatment decisions for MK.

AimsTo compare the long-term outcomes of deep anterior lamellar keratoplasty (DALK) with penetrating keratoplasty (PK) in keratoconus.MethodsRetrospective comparative case series (228 DALKs and 274 PKs). A biphasic linear model was used to describe the postoperative outcome of the endothelial cell density (ECD). Visual acuity, specular microscopy, corneal topography and optical coherence tomography findings were recorded.ResultsGraft survival of the 502 keratoconus eyes was 96.7 at 10 years and 95.6% at 20 years. Visual acuity improved from 20/378±5.1 lines preoperatively to 20/32±2.1 lines at 30 months. The corneal ECD decreased from 2494±382 cells/mm2 to 1521±659 cells/mm2 at 10 years. The mean simulated keratometry increased from 44.88±2.54 D at 1 year to 46.60±3.0 D at 3 years. The mean follow-up was 103.4 months for DALKs and 106.1 months for PKs. The cumulated incidence of postoperative ocular hypertension requiring treatment was significantly higher in PKs than in DALKs. The early- and late-phase rates of ECD loss were significantly lower in DALKs than in PKs. These figures in DALKs were 50% of those observed in PKs. The simulated mean keratometry was significantly higher in DALKs than in PKs in the mid but not in the long term. No significant differences in visual acuity were observed between both groups. Manual dissection-DALK featured slower visual recovery than PK and big bubble-DALK, whereas big bubble-DALK and PK featured similar visual recovery.ConclusionsDALK featuring higher endothelial survival and lower risk of postoperative ocular hypertension may be superior to PK when indicated for keratoconus.

Background/aimsThis study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops.MethodsAt our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and stored at 4°C. Platelet and leucocyte counts and transforming growth factor (TGF)-β1, epidermal growth factor (EGF), and fibronectin levels were assessed during storage for up to 4 weeks. Sterility was assessed by culturing 4-week poststorage samples. PRP, AS, and phosphate-buffered saline (PBS) eye-drop efficacies were compared using corneal epithelial wound healing assays in vitro and in vivo and monitoring wound areas under a microscope every 3 hours.ResultsHigher platelet and lower leucocyte counts were seen in PRP than in whole blood on the day of preparation. After storage, TGF-β1, EGF, and fibronectin levels were significantly higher in PRP than in AS eye-drops. In vitro and in vivo, PRP eye-drops used on the day of preparation significantly promoted corneal epithelial wound healing compared with PBS. Moreover, PRP eye-drops stored for 4 weeks significantly promoted corneal wound healing compared with PBS and AS eye-drops.ConclusionPRP eye-drops stored at 4°C for 4 weeks promoted corneal epithelial wound healing with higher levels of growth factors than those observed in AS eye-drops, while maintaining sterility, suggesting that this preparation satisfies the unmet medical needs in the treatment of refractory keratoconjunctival epithelial disorders.

AimsTo assess the impact of dry eye symptoms (DESs) on health-related quality of life (HRQOL) among Chinese residents.MethodsA total of 21 916 participants were involved in this nationwide cross-sectional study. All of them completed the Ocular Surface Disease Index-6 and the five-level European Quality of Life 5-Dimensional (EQ-5D) Questionnaire to assess the severity of DES and HRQOL, respectively. Multiple linear regression models were used to explore the associations of DES with EQ-5D health utility score (HUS) and visual analogue scale (VAS) score. We used logistic regression models to assess the relationships between DES and self-reported problems in the EQ-5D dimensions.ResultsOverall, 43.6% of participants reported DESs. Of them, 2511 (11.5%) were with mild symptoms, 2762 (12.6%) were with moderate symptoms and 4288 (19.6%) were with severe symptoms. Both EQ-5D HUS and VAS score were significantly negatively associated with the severity of DES. The difference in HUS between patients with no symptoms and severe symptoms (0.085) was larger than the minimally clinical important difference for EQ-5D. The loss in HRQOL was greater for patients with severe DES than those just with other comorbidities. Participants with DES had a significantly higher risk of reporting problems in all five EQ-5D dimensions, especially in pain/discomfort and anxiety/depression for patients with mild or moderate symptoms and in mobility, self-care and usual activities for severe patients.ConclusionPatients with more severe DES tend to have lower HRQOL. Effective interventions targeted at different HRQOL dimensions should be taken according to the severity of DES.

AimsTo evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures.Methods34 patients were enrolled in the study and underwent unilateral SMILE (21 of 34 patients) or unilateral tPRK (13 of 34 patients). Complete ophthalmic examinations, tear film function tests and Cochet-Bonnet esthesiometry were conducted to assess the effects of the surgeries on the corneal nerves and tear function. Morphological changes were assessed using in vivo confocal microscopy to evaluate the corneal sub-basal nerve plexus and dendritic cells. ELISA was used to measure the tear neuromediators. Clinical and morphological data at each follow-up point were compared with preoperative baseline values.ResultsAll patients who underwent unilateral SMILE or tPRK procedures exhibited bilateral corneal nerve degenerative changes, decreased corneal sensitivity, worsening of dry eye symptoms and changes in bilateral tear neuromediators. In the SMILE group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre length and negatively correlated with dendritic cell area. The dry eye severity was negatively correlated with corneal sensitivity. Tear levels of substance P and nerve growth factor were positively correlated with mean dendritic cell area and dry eye severity, but negatively correlated with corneal sensitivity. In the tPRK group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre density.ConclusionsUnilateral refractive surgery may bilaterally affect the morphology and function of corneal nerves and ocular surface status postoperatively.

AimsTo create and assess the performance of an artificial intelligence-based image analysis tool for the measurement and quantification of the corneal neovascularisation (CoNV) area.MethodsSlit lamp images of patients with CoNV were exported from the electronic medical records and included in the study. An experienced ophthalmologist made manual annotations of the CoNV areas, which were then used to create, train and evaluate an automated image analysis tool that uses deep learning to segment and detect CoNV areas. A pretrained neural network (U-Net) was used and fine-tuned on the annotated images. Sixfold cross-validation was used to evaluate the performance of the algorithm on each subset of 20 images. The main metric for our evaluation was intersection over union (IoU).ResultsThe slit lamp images of 120 eyes of 120 patients with CoNV were included in the analysis. Detections of the total corneal area achieved IoU between 90.0% and 95.5% in each fold and those of the non-vascularised area achieved IoU between 76.6% and 82.2%. The specificity for the detection was between 96.4% and 98.6% for the total corneal area and 96.6% and 98.0% for the non-vascularised area.ConclusionThe proposed algorithm showed a high accuracy compared with the measurement made by an ophthalmologist. The study suggests that an automated tool using artificial intelligence may be used for the calculation of the CoNV area from the slit-lamp images of patients with CoNV.