Purpose: To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information. Methods: The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added. Results: On the basis of revisiting the cellular origin of corneal dystrophy, a modified anatomic classification is proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial–stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. Most of the dystrophy templates are updated. The entity “Epithelial recurrent erosion dystrophies” actually includes a number of potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be differentiated from dystrophies such as TGFBI-induced dystrophies, which are also often associated with recurrent epithelial erosions. The chromosome locus of Thiel-Behnke corneal dystrophy is only located on 5q31. The entity previously designated as a variant of Thiel-Behnke corneal dystrophy on chromosome 10q24 may represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The so-called autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1). Confocal microscopy also has emerged as a helpful tool to reveal in vivo features of several corneal dystrophies that previously required histopathologic examination to definitively diagnose. Conclusions: This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophies more accurately classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer. Typical histopathologic and confocal images have been added to the corneal dystrophy templates.

Cystinosis is caused by mutations in the CTNS gene (17p13.2), which encodes for a lysosomal cystine/proton symporter termed cystinosin. It is the most common cause of inherited renal Fanconi syndrome in young children. Because of its rarity, the diagnosis and specific treatment of cystinosis are frequently delayed, which has a significant impact on the overall prognosis. In this document, we have summarized expert opinions on several aspects of the disease to improve knowledge and provide guidance for diagnosis and treatment.

Purpose.: To evaluate the relationship between the in vivo confocal microscopic (IVCM) morphology of subbasal corneal nerves, corneal sensitivity, and clinical parameters in patients with non-Sjögren dry eye disease (NSDD). Methods.: Forty-three patients with NSDD and 14 healthy age- and sex-matched control subjects were included. Each patient underwent an evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index (OSDI); tear film break-up time (TBUT); corneal and conjunctival staining (Oxford scale); the Schirmer test; corneal sensation testing using the Cochet-Bonnet esthesiometer; and corneal subbasal nerve analysis with IVCM. One eye of each subject was included in the study. Results.: Mean corneal sensitivity was significantly lower in the NSDD group as compared with the control group (P = 0.014). Corneal subbasal nerves showed significant changes in NSDD patients as compared with normal subjects: lower density (P < 0.001); increased tortuosity (P < 0.001); number of beadings (P < 0.001); and width (P = 0.041). In patients with NSDD, corneal subbasal nerve density was correlated to age (r = −0.352, P = 0.021); the Oxford scale (r = −0.486, P = 0.01); and central corneal sensitivity (r = 0.383, P = 0.041). The maximum length of nerve fibers within a frame (MaxL) was correlated to the OSDI (r = −0.265, P = 0.019) and the Oxford scale (r = −0.307, P = 0.039). In multivariate analysis after adjustment for age, corneal subbasal nerve density remained correlated to the Oxford score (P < 0.001). The Oxford score was also correlated to central corneal sensitivity (r = −0.304, P = 0.042). Conclusions.: NSDD patients have both structural and functional alterations of subbasal corneal nerves and these changes are related to the severity of dry eye.

Aim To investigate the association between dry eye symptoms and depression in an adult population. Methods In this population-based cross-sectional study, a random sample of 1957 subjects from the Beijing Eye Study was examined for dry eye disease (DED) in 2006. All patients completed an interviewer-assisted questionnaire on dry eye symptoms and underwent measurement of tear break-up time (TBUT), slit-lamp evaluation of corneal staining and meibomian gland dysfunction (MGD), and the Schirmer test. In 2011, 1456 subjects from this sample were evaluated for depression using a depression scale. The association between depression symptoms and dry eye clinical tests was evaluated. Results Definite depression was more prevalent in patients with DED than in subjects without DED (13.7±0.4% vs 8.6±0.3%, p=0.02). The depression score was correlated with dry eye symptoms (correlation coefficient r=0.07; p=0.013) but not with TBUT (p=0.18), the Schirmer test (p=0.37), corneal staining (p=0.30) and MGD evaluation (p=0.93). In multivariate regression analysis, the risk of definite depression remained significantly associated with dry eye symptoms (p=0.028) after adjusting for lower cognitive status (p=0.01), rural region of habitation (p=0.023) and lower body weight (p=0.05). Conclusions In an older population from Beijing, depression was associated with DED and in particular with dry eye symptoms.

The purpose of this study was to evaluate the relationship between the in vivo confocal microscopic (IVCM) morphology of subbasal corneal nerves and corneal sensitivity in patients with ocular surface disease. Ten healthy volunteers (control group), 12 patients with dry eye (dry-eye group), and 14 patients treated with IOP-lowering topical medications (glaucoma group) were included. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. IVCM of the cornea was performed and the following subbasal corneal nerves parameters were analyzed: density, number, width, number of beadings, number of branching, tortuosity, and reflectivity. One eye of each subject was included in the study. Corneal sensitivity was significantly decreased in dry-eye and glaucoma patients compared with controls. The density and number of subbasal corneal nerves were also significantly decreased in dry eye and glaucoma patients compared with controls. There was no difference in terms of subbasal nerve width, number of beadings, tortuosity, reflectivity, and number of branching between the dry-eye, the glaucoma, and the control groups. In all subjects, corneal sensitivity correlated positively with the density and number of subbasal nerves; however, in the dry-eye group, corneal sensitivity correlated with the density and the number of nerves, whereas in the glaucoma group, corneal sensitivity correlated only with the tortuosity of subbasal nerves. The relationship between corneal sensation and subbasal nerve morphology, as evaluated with IVCM, depends on the pathophysiological mechanism of ocular surface disease.