Computational protocol: Epithelial changes with corneal punctate epitheliopathy in type 2 diabetes mellitus and their correlation with time to healing

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Protocol publication

[…] A total of 928 patients received a diagnosis of CPE during the study period fromNovember 2010 to October 2015. Patientsfor whom CPE was attributed to multiple factors (a single causes could not be established, single cause include: dry eye; MGD; cataract extraction; drug; exposure) and who had undergone previous corneal or ocular surgery, had any ocular pathology other than diabetic retinopathy and keratopathy were excluded. One eye of each patient was selected for analysis, and in patients with bilateral CPE, the most severely affected eye was selected. The Ethics Committee of the Tongren Hospital (Beijing, China) approved the study.In all, 160 eyesfrom 160 patients with T2DMand CPE were eligible for inclusion in the study. The control group consisted of 149 eyesfrom 149 gender-, age- and aetiology-matched patients with CPE without T2DM who were seen during the study period.All patients underwent visual acuity testing as well as slit lamp biomicroscopic examination with fluorescein staining. A corneal specialist made the diagnosis of CPE based on a combination of symptoms and clinical signs and determined theaetiology. The symptoms included a combination of sharp pain, tearing, redness, foreign body sensation, photophobia and decreased vision combined with more than 5 spots of epithelial dots that stained with fluorescein []. Other data collected included age, sex, affected eye, worse affected eye, history of surgery, use of ocular medication, presence of MGD and T2DM. T2DM was diagnosed based on the standards of medical care in diabetes [].CPE was divided into the following aetiological categories:Dry eye related: normal eye lid margin with tear film break up time (TFBUT) <5 s, Schirmer1test < 5 mm/5 min [];Meibomian gland disease (MGD) related: patients with lid signs of MGD [];Cataract extraction related: CPE occurring within 2 weeks of surgery in the absence of medication use (as detailed below), dry eye or MGD.Drug related: CPE in those using eye drops (tobramycin or dexamethasone) or ganciclovir gel for more than 1 month and absence of dry eye and MGD;Exposure related: CPE resulting from corneal exposure with corneal staining located inferiorly in the area of exposure, in the absence of dry eye and MGD.Dry eye related: normal eye lid margin with tear film break up time (TFBUT) <5 s, Schirmer1test < 5 mm/5 min [];Meibomian gland disease (MGD) related: patients with lid signs of MGD [];Cataract extraction related: CPE occurring within 2 weeks of surgery in the absence of medication use (as detailed below), dry eye or MGD.Drug related: CPE in those using eye drops (tobramycin or dexamethasone) or ganciclovir gel for more than 1 month and absence of dry eye and MGD;Exposure related: CPE resulting from corneal exposure with corneal staining located inferiorly in the area of exposure, in the absence of dry eye and MGD.All patients underwent IVCM in both eyes using the Heidelberg Retina Tomograph III Rostock Cornea Module (HRT III RCM; Heidelberg Engineering GmbH, Heidelberg, Germany). Genteal Gel (0.2% carbomer eye drops; Dr. Gerhard Mann, Chem.-Pharm, Fabrik GmbH) was applied in a disposable sterile polymethylmethacrylate cap (Tomo-Cap; Heidelberg Engineering GmbH)placed on the tip of the objective lens. A drop of local anaesthetic (0.4% tetracaine hydrochloride) was administered to both eyes and the subject was asked to fixate on a distant target before commencing scanning of the central cornea. A single experienced and masked examiner performed all scans. Section scans of the central cornea were recorded with the Heidelberg HRT-III microscope, using 384 × 384 pixels and a field of view of 400 × 400 μm2.One randomly selected eye from each person in the control group was used for analysis. Three good quality images of the LC, SBN and BEC were selected and were used for image analysis by the examiner. The average of three measurements was used for further comparative analysis []. The basal epithelium was defined as the first three clear scans anterior to Bowman’s layer. BEC was measured manually using HRT III proprietary software.On average, three quality images of Bowman’s layer were used to quantify both Langerhans cell density and nerve fibre morphology in all patients and controls, and the average results of all these images were calculated. SBN density was defined as the total nerves lengths in units of mm/mm2 []. SBN was analysed in three selected high-quality images using NeuronJ software (Erik Meijering). NeuronJ is an ImageJ (National Institutes of Health, Bethesda, MD) plugin to facilitate the tracing and quantification of elongated image structures [].The therapy for CPE was standardized and included sodium hyaluronate eye drops and de-proteinized calf blood extract eye gel 4 times a day []. All patients were examined within 3-7 days of the initiation of treatment and at a similar interval thereafter untill healing was complete.The healing time was defined as the number of days from the onset of treatment to the day the corneal epithelial fluorescein staining became negative. An example of a patient with T2DM who developed CPE following cataract surgery is shown in Fig. . Corneal staining resolved 21 days after the initiation of treatment.Fig. 1All statistical analyses were performed with SPSS (version 18.0). Chi-square analysis, two samples rank sum test, Pearson correlation and multiple linear regression were used. P < 0.05 was considered to be statistically significant. […]

Pipeline specifications

Software tools NeuronJ, ImageJ
Application Microscopic phenotype analysis
Organisms Homo sapiens
Diseases Cataract, Corneal Diseases, Diabetes Mellitus, Liver Diseases, Dry Eye Syndromes