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INTRODUCTION/AIMS: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively. METHODS: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 µm2 ). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 µm) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls. RESULTS: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03). DISCUSSION: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.

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PURPOSE: To investigate small nerve fibre damage and inflammation at the level of the sub-basal nerve plexus (SNP) of severe obese patients and compare the results with those of healthy subjects. METHODS: This cross-sectional, observational study investigated the data of 28 patients (14 out of 28 prediabetic or diabetic) with severe obesity (Body Mass Index; BMI ≥ 40) and 20 healthy subjects. Corneal nerve fibre density (CNFD), branch density (CNBD), fibre length (CNFL), nerve fibre area (CNFA), nerve fibre width (CNFW), and nerve fractal dimension (CNFrD) and dendritic cell (DC) density were evaluated using in vivo confocal microscopy (IVCM, Heidelberg Retinal Tomograph III Rostock Cornea Module). Automatic CCMetrics software (University of Manchester, UK) was used for quantitative analysis of SNP. RESULTS: Mean age was 48.4±7.4 and 45.1 ± 5.8 in the control and obese group, respectively (p = 0.09). Mean BMI were 49.1 ± 7.8 vs. 23.3 ± 1.4 in obese vs. control group, respectively (p < 0.001). Mean CNFD, CNBD, CNFL, CNFA, CNFW were significantly reduced in obese group compared with those in the control group (always p < 0.05, respectively). There were no significant differences in any ACCMetrics parameters between prediabetic/diabetic and non-diabetic obese patients. Increased DC densities were detected in obese group compared with those in control group (p < 0.0001). There were significant correlations between BMI scores and SNP parameters. CONCLUSION: Imaging with IVCM is a feasible, non-invasive method to detect and quantify occult corneal nerve damage and increased inflammation in patients with obesity. This study suggests that obesity may be a separate risk factor for peripheral neuropathy regardless of DM.

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PURPOSE: The effect of body mass index (BMI) and central fat distribution (CFD) reduction after bariatric surgery on ocular refraction is not well established. We assessed association between anthropometric parameters and refraction errors with other ocular and metabolic parameters 1 year after the surgery. MATERIALS AND METHODS: This was a retrospective study with patients underwent bariatric surgery and had at least 1 year follow-up. Data were extracted from the bariatric and ophthalmology outpatient clinic records of the participants. Measurements of metabolic, anthropometric, and ocular parameters including BMI, CFD, refraction status, visual acuity, intraocular pressure (IOP), optic coherence tomography (OCT), and biometry test of the eyes were evaluated. RESULTS: Seventy-four eyes of 37 patients had a mean follow-up of 14.4 ± 1.7 months after the surgery. Mean BMI and percentage of CFD decreased from 47.5 ± 6.7 to 33.1 ± 5.2 kg/m2 (p < 0.01) and 28.5 ± 5.74 to 17.8 ± 4.64 (p < 0.001) after 1 year, respectively. Mean refractive errors of the right and left eyes changed from - 0.62 ± 1.23 D to - 0.17 ± 1.36 D and from - 0.79 ± 1.39 to - 0.34 ± 1.56 after 1 year of the surgery (p < 0.001). Mean IOP was significantly reduced (p < 0.001). Unlike BMI, reduction in CFD was significantly correlated with refraction change in both eyes (right eyes; r = 0.783, left eyes; r = 0.791, p < 0.001) after 1 year. No significant differences were found in the other parameters. CONCLUSION: Bariatric surgery induced significant refractive change in eyes, which is significantly associated with CFD reduction after 1 year. Bariatric surgery should be considered as a risk factor in patients with unexpected refractive error changes.

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PURPOSE: To report a case of crystalline keratopathy induced the Dieffenbachia plant sap. METHODS: Case report and review of the literature. RESULTS: A 38-year-old woman presented with redness, irritation, and slightly blurred vision in the right eye after the exposure of Dieffenbachia plant sap to her right eye. The patient's eye was irrigated with copious saline on her admission. On ophthalmic examination, her visual acuity was 20/32 OD and 20/20 OS. Anterior segment examination of the right eye revealed mild eyelid edema, grade 2 conjunctival hyperemia, diffuse punctate corneal epithelial erosions, mild stromal edema, and fine refractile needle-like crystals extending from the subepithelial region to mid-stroma. The crystals were visualized with anterior segment photographs and in vivo corneal confocal microscopy (IVCCM) views. Moxifloxacin 0.5% and preservative-free artificial tears were started. Loteprednol etabonate 0.5% was added once the epithelial erosions had healed. The corneal crystals were completely disappeared and the visual acuity of the patient was 20/20 in the third week's visit. CONCLUSIONS: Patients with a history of contact with plant sap should be irrigated with abundant saline immediately to reduce the effect of chemical trauma and thus reduce mechanical damage by inhibiting crystal penetration. IVCCM offers a non-invasive, fast, and reliable diagnosis of Dieffenbachia-related injury, especially in patients with ocular irritation of unknown etiology. Besides, IVCCM is very valuable to differentiate calcium oxalate crystals from other crystalline corneopathies.

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PURPOSE: Ocular discomfort is a common symptom in central sensitization syndromes. The aim of this study was to evaluate ocular surface discomfort and related corneal changes in patients with irritable bowel syndrome. METHODS: Twenty-nine patients with IBS (20 female, 9 male, mean age: 45.3 ± 10.1 years) and 37 healthy control subjects (25 female, 12 male, mean age: 44.95 ± 9.76 years) were included. A detailed ophthalmological examination was performed to all participants including tear break-up time (TBUT) and Schirmer test I with anesthetic (SIT). Ocular discomfort was evaluated using the ocular surface disease index (OSDI) questionnaire and corneal sensation was evaluated with Cochet-Bonnet esthesiometer. Corneal subbasal nerve plexus was evaluated with in vivo corneal confocal microscopy (IVCM). RESULTS: There was no significant difference between the groups for age, gender distribution, and visual acuity. OSDI scores were significantly higher (p = 0.008) and TBUT was significantly reduced in patients with IBS compared to controls (p = 0.001 for right eye, p = 0.014 for left eye). However, there was no significant difference in corneal touch sensation and SIT results between the groups. IVCM revealed that corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length were significantly reduced in patients with IBS (p < 0.001, p < 0.001, and p = 0.023, respectively). CONCLUSION: Patients with IBS have increased dry eye-associated ocular surface complaints and nerve fiber loss in corneal subbasal nerve plexus. IBS should be remembered in the differential diagnosis, when there is discordance between the level of ocular surface discomfort and dry eye disease associated corneal findings.

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PURPOSE: Our goal is early detection of neuropathy in patients with type 2 diabetes with or without microalbuminuria in the absence of diabetic retinopathy and peripheral neuropathy by using in vivo corneal confocal microscopy (IVCCM). METHODS: A total of 60 type-2 diabetic patients, assigned to either a diabetes mellitus (DM) with microalbuminuria group (DM/MA+, n=30) or a DM without microalbuminuria group (DM/MA-, n=30), and 30 age-matched control subjects were enrolled in this study. All cases underwent evaluation of blood glucose level, HbA1c, lipid fractions, body mass index (BMI), and corneal sensitivity (CS). Corneal nerve fiber length (NFL), nerve fiber density (NFD), nerve branch density (NBD), and tortuosity coefficient (TC) were quantified by IVCCM. None of the patients had peripheral neuropathy or retinopathy. RESULTS: Compared with the healthy subjects, NFL and NFD were reduced in both diabetic groups (P<0.0001), while NBD was significantly reduced in the DM/MA+ group. Between the diabetic groups, NFL, NFD, and NBD were significantly higher in the DM/MA- group (all P's<0.001). CS was significantly lower in DM/MA+ compared with DM/MA- and controls (both P's<0.0001). NFD and NFL were inversely correlated with age, triglyceride level, and BMI. CONCLUSION: These results indicate that significant damage to small nerves, quantified using IVCCM, can be detected in the absence of retinopathy, peripheral neuropathy or microalbuminuria in type 2 diabetic patients. The severity of corneal nerve involvement may further increase in the presence of nephropathy. This feature may also be valuable for early detection of microvascular complications of DM, allowing for the prevention of progression of life threatening microvascular complications.

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BACKGROUND: This study aimed to determine the prevalence of psychiatric disorders in patients with keratoconus and the effect of clinical parameters and psychiatric morbidity on quality of life in this patient group. MATERIALS AND METHODS: This cross-sectional study enrolled 94 patients with keratoconus. All patients underwent a complete ophthalmic and psychiatric examination and completed the The National Eye Institute Refractive Error Quality of Life Instrument-42 (NEI-RQL-42), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) questionnaires. The current diagnosis of psychiatric disorders was determined using the Structured Clinical Interview for DSM-IV (SCID). The impact of disease severity (binocular BCVA ≥0.4 logMAR, steep K reading ≥52, and Amsler-Krumeich grades) on vision-related quality of life was also analyzed. RESULTS: The patients' mean age was 23.9 ± 4.8 (range, 18-40) years. Of the 94 participants 35 (37.2%) had a psychiatric diagnosis, 13 (13.8%) had moderate-severe depression and 20 (21.2%) had moderate-severe anxiety according to the BDI and BAI, respectively. The probability of having a psychiatric disorder was higher if the keratoconus was more severe. Patients with a psychiatric diagnosis scored lower on physical functioning, role limitations due to emotional problems, energy/fatigue; emotional well-being, social functioning and pain subscales of the Short Form-36 (SF-36). Having a SCID-1 psychiatric diagnosis and the presence of a psychiatric disorder did not significantly affect NEI-RQL-42 questionnaire scores. CONCLUSIONS: There was high psychiatric morbidity among patients with keratoconus. Having a psychiatric disorder was associated with lower QoL as measured using the SF-36.

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PURPOSE: To evaluate reading performance, preferred reading distance, and spectacle independence in patients implanted with a low add multifocal or an extended depth of focus (EDOF) intraocular lens (IOL) after phacoemulsification. METHODS: In this prospective study, patients were randomized into two groups: the diffractive multifocal Tecnis + 2.75 D (ZKB00) IOL (Tecnis + 2.75 group; 15 patients) or the EDOF Tecnis Symfony (ZXR00) IOL (Symfony group; 14 patients) for bilateral implantation with mini-monovision. Reading performance parameters (reading acuity [RA], critical print size [CPS], and maximum reading speed [MRS]) were evaluated with MNREAD acuity charts at 40 cm, and preferred reading distances and spectacle independence for near activities were assessed preoperatively and at the postoperative 1st, 3rd, and 6th months. RESULTS: At the postoperative 6th month, binocular logMAR UNVA and DCNVA were significantly better in the Symfony group than in the Tecnis + 2.75 group (UNVA: 0.15 ± 0.07 vs. 0.22 ± 0.08, p = 0.046; DCNVA: 0.21 ± 0.05 vs. 0.28 ± 0.07, p = 0.043; respectively). There was no significant difference in reading performance parameters between the groups; however, the Symfony group preferred significantly closer reading distance than the Tecnis + 2.75 group (42.00 ± 4.67 cm; 45.87 ± 5.32 cm, respectively, p = 0.030). At the postoperative 6th month, 14.3% and 26.7% of patients reported that they needed spectacles, rarely or occasionally, for near activities in the Symfony and Tecnis + 2.75 groups, respectively (p > 0.05). CONCLUSIONS: When implanted with mini-monovision, although functional near visual acuity and a high degree of spectacle independence at near distances were achieved with both IOLs, patients implanted with the EDOF IOL preferred closer reading distance than those implanted with the low add diffractive multifocal IOL.

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OBJECTIVE: To determine the short-term effect of contact lens (CL) wear on the self-concept of adolescents. METHODS: In this open-label trial, first-time CL wearing adolescents were prescribed Delefilcon A (DAILIES TOTAL1,® Alcon, USA) daily disposable CL. To determine the self-concept level of the subjects at dispensing and after one month, the Turkish adapted version of the Piers-Harris Children's Self-Concept Scale (PHCSCS) was used. The subject-reported outcomes included lens wettability, vision quality, comfort, and overall satisfaction. Self-concept was evaluated under six categories. RESULTS: The mean age of the 21 subjects was 16.5 ± 1.5 years. All subjects had normal biomicroscopic assessments and best corrected visual acuity was 20/20. The mean spherical equivalent was -2.90 ± 1.18 (range, -4.75 to -1.75). Spectacle use was causing dissatisfaction with their appearance in 90% of subjects (n = 19), the others defined it as uncomfortable. Most subjects had acquired information about CLs from their peers and friends (57%, n = 12). Most of the subscales in the PHCSCS showed increased but statistically insignificant scores after one month. The mean overall satisfaction was 95%. CONCLUSION: Prescription of CLs may be a good option in adolescents even if the self-concept did not show significant improvement in the short term.

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The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe DED. Designed as an international, multicenter study, 16 patients with symptoms of at least an Ocular Surface Disease Index (OSDI) score of 33, and corneal fluorescein staining (CFS) of at least Oxford grade 3, were included and randomized into two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the baseline visit, and after eight weeks, the subbasal nerve plexus of 16 patients were assessed by confocal laser scanning microscopy (CSLM). The images were submitted to a masked reading center for evaluation. Results showed a significant increase of total nerve fiber lengths (CNFL) in the HMWHA group (p = 0.030) when compared to the control group, where the total subbasal CNFL did not significantly change from baseline to week 8. We concluded that in severe DED patients, HMWHA from topically applied eye drops could cross the epithelial barrier and reach the subbasal nerve plexus, where it exercised a trophic effect.

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PURPOSE: To compare the efficacy and safety of accelerated corneal cross-linking (CXL) with conventional CXL in pediatric patients with keratoconus. METHODS: Consecutive patients with keratoconus received either accelerated CXL (9 mW/cm2 irradiance for 10 minutes) or conventional CXL (3 mW/cm2 irradiance) for 30 minutes. Visual acuities (uncorrected [UDVA] and corrected [CDVA] distance visual acuity, logMAR), spherical error, cylindrical error, spherical equivalent, and keratometric values were recorded. Follow-up measurements were compared with baseline values. RESULTS: The study enrolled 48 eyes: 22 eyes had accelerated CXL (mean age: 16.0 ± 1.7 years) and 26 eyes had conventional CXL (mean age: 15.7 ± 1.6 years). Compared with preoperative values, all mean keratometric values significantly improved in the accelerated CXL group (flat [K1]: Δ = -0.64 D, P < .0001, steep [K2]: Δ = -0.63 D, P = .009 and Kmax: Δ = -0.55 D, P = .028), but no significant changes were observed in the mean UDVA and CDVA. In the conventional CXL group, all mean keratometric values and CDVA significantly improved (K1: Δ = -0.65 D, P = .017, K2: Δ = -0.87 D, P = .006, Kmax: Δ = -1.47 D, P = .011). No significant changes were observed in refractive error in either CXL group. There were no significant differences in the keratometric readings, visual acuities, or refractive error between the two groups at the 2-year follow-up. CONCLUSIONS: Both conventional and accelerated CXL protocols appear to be effective in stabilizing keratoconus progression in pediatric patients. Improved CDVA was also observed in the conventional CXL group. Accelerated CXL, with its advantage of shorter treatment duration, may be an alternative in pediatric patients. [J Refract Surg. 2020;36(4):265-269.].

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PURPOSE: To evaluate the changes in corneal epithelial thickness and corneal anterior and posterior curvatures during the day, and the effect of wearing daily disposable soft contact lenses. METHODS: Thirty-two healthy volunteers were enrolled in a randomized crossover study. At the baseline visit, corneal and epithelial thickness maps (OCT; Optovue, Inc., Fremont, CA, USA) and keratometric measurements (Pentacam, Oculus, GmbH, Germany) were performed in the morning and in the afternoon (8 hours after). Then, each subject was fitted with the following brands of daily disposable contact lenses in random order: Dailies Total 1 (Delefilcon A), Dailies Aqua Comfort (Nelfilcon A), TruEye (Narafilcon A) and Biotrue Oneday (Nesofilcon A) on different days. All fitted lenses had a power of -3.00 diopters (D). Measurements were repeated before putting the contact lens on and after an-eight-hour contact lens wear. RESULTS: With no lens wear, the anterior topographic indices showed significant steepening [Kflat: p < 0.0001; Ksteep: p < 0.0001 and maximum keratometry value (Kmax): p = 0.04] and the corneal thickness significantly decreased in the central and temporal portion of the cornea in the afternoon. There were no significant changes in the posterior topographical indices and corneal epithelial thickness. With contact lens wear, no significant change occurred in the corneal and epithelial thickness, and the anterior and posterior curvatures during the day (all p values >0.05). There was no statistically significant difference in the epithelial thickness among the groups wearing different contact lens types (p > 0.05). CONCLUSIONS: Anterior corneal topographic indices steepen depending on the natural diurnal variations. Daily wear of soft contact lenses appears to mask this steepening. The corneal epithelial thickness is not affected by daily disposable soft contact lenses.

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PURPOSE: The aim of the study was to assess the efficacy of a topical regenerating agent (RGTA) for management of persistent epithelial defects (PEDs) resistant to conventional therapy. METHODS: Twenty-one patients (23 eyes) with PEDs despite the use of conventional therapy for lagophthalmos (n = 4), neurotrophic ulcer (n = 9), chemical burn (n = 3), Stevens-Johnson syndrome (n = 1), atopic keratoconjunctivitis (n = 1), severe dry eye (n = 2), peripheral ulcerative keratitis (n = 1), fungal keratitis (n = 1), and bacterial keratitis (n = 1) were enrolled in the study. Patients were treated with RGTA (Cacicol; Thea, Paris, France) instilled at a dosage of one drop on alternate days. Patients were evaluated by slit-lamp examination, anterior segment photography, and fluorescein-dye testing. Ulcer areas were noted on alternate days starting from the first day of instillation. RESULTS: Twenty of 23 eyes (86.9%) displayed complete corneal healing after a mean period of ∼7.2 days (range, 2-20 days). Mean decrease ratio of ulcer area observed was 61.2% (range, 8.8%-100%, n = 19) on the 2nd day, 74.4% (range, 36%-100%, n = 16) on the 4th day, 80.2% (range, 43.7%-100%, n = 12) on the 6th day, 88.5% (range, 55.9%-100%, n = 9) on the 8th day, and 85.5% (range, 58.3%-100%, n = 7) on the 10th day. No significant differences were found in the epithelialization speed between eyes with and without bandage contact lenses in any postoperative day (P > 0.05). There were no treatment-related local or systemic side effects during the study. CONCLUSIONS: RGTA seems to be an effective therapeutic alternative in the treatment of persistent corneal epithelial defects.

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PURPOSE: To evaluate the lens edge interaction with the ocular surface with different edge designs using optical coherence tomography and to examine the effect of lens power on the lens edge interactions. METHODS: Four types of silicone hydrogel lenses with different edge designs (round-, semi-round-, chisel-, and knife-edged) at six different powers (+5.0, +3.0, +1.0, -1.0, -3.0, and -5.0 diopters) were fitted to both eyes of 20 healthy volunteers. Optical coherence tomography images were taken at the corneal center and at the limbus within 15-30 minutes after insertion. The images were evaluated with respect to two parameters: conjunctival indentation exerted by the lens edge; and the tear film gaps between the posterior surface of the lens and the ocular surface. The amount of conjunctival indentation was measured with the distortion angle of the conjunctiva at the lens edge. RESULTS: The degree of conjunctival indentation was highest with the chisel-edged design followed by the semi-round design (P<0.0001). Knife- and round-edged lenses exerted similar levels of conjunctival indentation that was significantly lower compared to chisel-edged lens (P<0.001). For each one of the tested lens edge designs, no significant difference was observed in the conjunctival indentation with respect to lens power. The chisel-edged lens produced the highest amount of conjunctival indentation for each one of the six lens powers (P<0.0001). Post-lens tear film gaps at the limbus were observed at most in the round-edge design (P=0.001). CONCLUSION: The fitting properties of contact lenses may be influenced by their edge design but not by their lens power.

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PURPOSE: To evaluate the accuracy of intraocular lens (IOL) power calculation using an optical low-coherence reflectometry (OLCR) biometer and to compare the results with those obtained with an immersion ultrasound biometry (IUB). METHODS: Biometric measurements were obtained with OLCR and IUB combined with automated keratometry before cataract surgery. The mean prediction error (MPE) and the mean absolute error (MAE) were calculated for five various IOL formulas (SRK II, SRK/T, Holladay, Hoffer Q, and Haigis), and the two different biometry methods were compared. RESULTS: Optical low-coherence reflectometry measured a slightly longer axial length (mean difference, 0.05 mm; P<0.001) and a shallow anterior chamber depth (mean difference, 0.12 mm; P<0.001). With OLCR, the MPEs (±SD) calculated by the SRK II, SRK/T, Holladay, Hoffer Q, and Haigis formulas were -0.04 ± 0.53, -0.04 ± 0.56, -0.03 ± 0.53, -0.04 ± 0.56, and -0.02 ± 0.56, respectively (P<0.0001). The mean differences (± SD) for MAE were statistically significant between OLCR and IUB; SRK II (0.47 ± 0.44 vs. 0.61 ± 0.49, P<0.0001), SRK/T (0.39 ± 0.4 vs. 0.49 ± 0.45, P=0.0004), Holladay (0.37 ± 0.37 vs. 0.47 ± 0.41, P<0.0001), Hoffer Q (0.4 ± 0.39 vs. 0.5 ± 0.43, P<0.0001), and Haigis (0.4 ± 0.39 vs. 0.7 ± 0.51, P<0.0001). CONCLUSION: The OLCR produces a more predictable refractive outcome than IUB, with patients' spherical equivalent being more likely to be closer to their target refraction.

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A 6-year-old boy was referred to our hospital with orbital cellulitis. He had a history of 7 days of fever despite antibiotherapy. At first, he only had pharyngitis and conjunctivitis, but then an orbital mass evolved which restricted the movement of his right eye and there was also periorbital inflammation resembling orbital cellulitis. Examination at presentation revealed conjunctivitis with secretion, periocular inflammation and edema, right-preauricular lymphadenopathy and restriction of upgaze in the right eye. Laboratory findings included a white blood cell count of 19,000 cells per mm3, with 81.5% neutrophils, 15.0% lymphocytes, 1.2% monocytes and 0.4% basophils. The erythrocyte sedimentation rate was 52 mm/h and the C-reactive protein level was 46.3 mg/dl. Magnetic resonance imaging confirmed orbital cellulitis and pansinusitis. Vancomycin (60 mg/kg/day) and meropenem (100 mg/kg/day) were administered, but desquamation on his fingertips and a rash appeared on the tenth day. A pediatric consultation resulted in a diagnosis of incomplete Kawasaki disease (KD). After administration of aspirin, the orbital inflammation regressed in 3 days. No coronary artery lesions were detected on the first echocardiography, but these did appear 6 weeks later. This confirmed the KD diagnosis.