Increased corneal sub-basal nerve density in patients with Sjögren syndrome treated with topical cyclosporine A.

BACKGROUND: To evaluate quantitative and qualitative changes in sub-basal corneal nerves (SBN) via in vivo confocal microscopy in patients with Sjögren syndrome dry eye (SSDE) treated with topical cyclosporine A (CsA). DESIGN: Prospective, observational, non-randomized study. PARTICIPANTS: Thirty eyes of 30 patients with SSDE refractory to conventional treatment treated with CsA 0.05% twice daily for 6 months. Fifteen eyes of 15 healthy, age and gender matched, volunteers constituted the control group at baseline. METHODS: A clinical evaluation of dry eye, corneal sensation using Cochet-Bonnet esthesiometry and in vivo confocal microscopy analysis of the central cornea were performed prospectively at baseline for all patients, and after 6 months of treatment with CsA. MAIN OUTCOME MEASURES: Density, number, reflectivity and tortuosity of SBN, dendritic cell (DC) density, esthesiometry, and dry eye signs and symptoms. RESULTS: Topical CsA 0.05% improved clinical signs and symptoms, and increased corneal sensitivity. Following treatment, SBN density was significantly increased (P < 0.0001) associated with a decreased in DC density (P < 0.0001). The increase in SBN density after treatment was positively correlated with baseline SBN density (R2  = 0.33; P = 0.0008) and negatively correlated with baseline Ocular Surface Disease Index (R2  = 0.28; P = 0.002), Oxford score (R2  = 0.31; P = 0.002), and DC density (R2  = 0.37; P = 0.0003). CONCLUSIONS: Topical CsA led to an increase in corneal SBN density, improving clinical signs and symptoms of SSDE. Our results also suggest an improved response to treatment in patients with less initial nerve damage.

Decreased Corneal Sensation and Subbasal Nerve Density, and Thinned Corneal Epithelium as a Result of 360-Degree Laser Retinopexy.

PURPOSE: To assess the effects of 360-degree laser retinopexy on human corneal subbasal nerve plexus and to investigate correlations among corneal subbasal nerve plexus density, corneal epithelial thickness, and corneal sensitivity. DESIGN: Prospective, observational, nonrandomized study. PARTICIPANTS: A total of 15 eyes of 15 patients who underwent pars plana vitrectomy (PPV) with 360-degree laser retinopexy for retinal detachment (RD) and 15 eyes of 15 patients who underwent PPV for macular hole (MH) without laser treatment. METHODS: Corneal sensation, corneal epithelial thickness, and corneal subbasal nerve plexus density were assessed before surgery and 6 months after surgery via in vivo confocal microscopy, anterior segment optical coherence tomography (AS-OCT), and Cochet-Bonnet esthesiometry (Luneau Ophthalmologie, Paris, France). MAIN OUTCOME MEASURES: Corneal subbasal nerve plexus density, corneal epithelium thickness, and central corneal sensitivity. RESULTS: Compared with baselines values, the mean subbasal nerve density (P < 0.001), mean corneal epithelium thickness (P = 0.006), and mean corneal sensitivity (P < 0.001) in the RD group were significantly decreased 6 months after surgery by 74.3%, 4.7%, and 56.6%, respectively. Conversely, in the MH group there were no significant differences in the mean subbasal nerve density (P = 0.34), mean corneal epithelial thickness (P = 0.19), and mean corneal sensitivity (P = 0.42) between preoperative and 6-month postoperative values (0.7%, 0.4%, and 0.8%, respectively). The postoperative decrease in corneal subbasal nerve density after laser retinopexy was associated with a decrease in corneal epithelium thickness (r(2) = 0.42; P = 0.006) and a decrease in corneal sensitivity (r(2) = 0.48; P = 0.004). The postoperative decrease in corneal sensitivity poorly correlated with the decrease in corneal epithelial thickness (r(2) = 0.24; P = 0.045). Postoperative corneal nerve density decreased as total laser energy increased (r(2) = 0.51; P = 0.002). CONCLUSIONS: Subbasal corneal nerve plexus density decreases after 360-degree laser retinopexy and is accompanied by epithelium thinning and decreased corneal sensation. Surgeons should eschew heavy confluent retinal laser treatment, and corneal sensitivity should be assessed postoperatively to determine whether significant anesthesia has occurred. In such instances, prophylactic measures may be warranted against the development of neurotrophic ulcers.

Anatomic Predictive Factors of Acute Corneal Hydrops in Keratoconus: An Optical Coherence Tomography Study.

PURPOSE: To define the optical coherence tomography (OCT) corneal changes predisposing to acute corneal hydrops among patients with advanced keratoconus. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 191 advanced keratoconic eyes from 191 patients with advanced keratoconus cases were studied. METHODS: Data collected from patients with advanced keratoconus cases were studied during a minimum period of 24 months of follow-up. High-resolution Fourier-domain corneal OCT (5 µm of axial resolution) and corneal topography were performed every 4 months during the follow-up. Several anatomic features at the keratoconus cone were analyzed with OCT, including epithelial and stromal thicknesses, the aspect of Bowman's layer, the presence of Vogt's striae, and stromal opacities. A comparative analysis between anatomic corneal features in eyes that developed corneal hydrops and those that did not develop this complication during the follow-up was performed. MAIN OUTCOME MEASURES: Evaluation of anatomic corneal changes at risk of developing a corneal hydrops on the basis of OCT findings. RESULTS: Eleven cases of corneal hydrops (5.8%) occurred in our series during a mean follow-up of 30 months (24-36 months). All of these patients were male and younger (23.7±5.9 years) than patients with no acute keratoconus (32.7±11.3 years). Increased epithelial thickening with stromal thinning at the conus and the presence of anterior hyperreflectives at the Bowman's layer level were significantly associated with corneal hydrops, whereas the presence of corneal scarring was a preventive factor. At the healing stage, a pan-stromal scar occurs, with a significant stromal thickening and cornea flattening. CONCLUSIONS: Increased epithelial thickening, stromal thinning at the keratoconus cone, anterior hyperreflectives at the Bowman's layer level, and the absence of stromal scarring are associated with a high risk of developing corneal hydrops. These aspects should be taken into account by the clinician in the evaluation of keratoconus eyes and in the planning of corneal keratoplasty.

Fourier-domain optical coherence tomography imaging in keratoconus: a corneal structural classification.

OBJECTIVE: To study corneal morphologic changes in a large keratoconic population and to establish a structural optical coherence tomography (OCT) classification. DESIGN: Cross-sectional, observational study. PARTICIPANTS: A total of 218 keratoconic eyes from 218 patients and 34 eyes from 34 normal subjects. METHODS: A Fourier-domain OCT system with 5-µm axial resolution was used. For each patient, 3 high-resolution scans were made across the keratoconus cone. All scans were analyzed by keratoconus specialists who were not given access to patients' clinical and topographic data, and who established an OCT classification. The reproducibility of the classification and its correlation with clinical and paraclinical characteristics of patients with keratoconus were evaluated. The OCT examinations were performed every 4 months to follow up structural corneal changes. MAIN OUTCOME MEASURES: Evaluation of the structural corneal changes occurring in keratoconus cases with various stages of severity based on OCT findings. RESULTS: Fourier-domain OCT classification containing 5 distinct keratoconus stages is proposed. Stage 1 demonstrates thinning of apparently normal epithelial and stromal layers at the conus. Stage 2 demonstrates hyperreflective anomalies occurring at the Bowman's layer level with epithelial thickening at the conus. Stage 3 demonstrates posterior displacement of the hyperreflective structures occurring at the Bowman's layer level with increased epithelial thickening and stromal thinning. Stage 4 demonstrates pan-stromal scar. Stage 5 demonstrates hydrops; 5a, acute onset: Descemet's membrane rupture and dilaceration of collagen lamellae with large fluid-filled intrastromal cysts; 5b, healing stage: pan-stromal scarring with a remaining aspect of Descemet's membrane rupture. The reproducibility of the classification was very high between the corneal specialist observers. Clinical and paraclinical characteristics of keratoconus, including visual acuity, corneal epithelium and stromal thickness changes, corneal topography, biomechanical corneal characteristics, and microstructural changes observed on confocal microscopy, were concordant with our OCT grading. CONCLUSIONS: Optical coherence tomography provides an accurate assessment of structural changes occurring in keratoconus eyes. These changes were correlated with clinical and paraclinical characteristics of patients. The established classification not only allows structural follow-up of patients with keratoconus but also provides insight into the pathogenesis of keratoconus and treatment strategies for future research.

Corneal epithelial thickness mapping using Fourier-domain optical coherence tomography for detection of form fruste keratoconus.

PURPOSE: To determine whether optical coherence tomography (OCT) epithelial mapping can improve the detection of form fruste keratoconus. SETTING: French National Eye Hospital, Paris 6 Pierre & Marie Curie University, Paris, France. DESIGN: Retrospective comparative study. METHODS: Eyes with normal corneas, form fruste keratoconus, moderate keratoconus, or severe keratoconus were assessed using Fourier-domain OCT (RTVue 5.5), scanning-slit corneal topography (Orbscan IIz), and rotating Scheimpflug camera (Pentacam Comprehensive Eye Scanner). Several parameters provided by the software or derived from elevation maps, OCT pachymetric maps, and OCT epithelium parameters were evaluated and compared between the 4 groups. RESULTS: The study involved 145 eyes. There were no significant differences in the keratometry (K) value, inferior-superior value, keratoconus index, central K index, and topographic keratoconus classification indices between the form fruste keratoconus group and the control group (P > .05). Form fruste keratoconic corneas had less epithelial thickness in the thinnest corneal zone than normal corneas, and greater epithelial thickness in the thinnest corneal zone than keratoconic corneas (P < .005). The epithelial thickness in the thinnest corneal zone in form fruste corneas was located inferiorly (P < .005) and corresponded with the zone of minimum epithelial thickness and maximum posterior elevation (P < .005). The receiver operating characteristic curve analysis showed good overall predictive accuracy of the epithelial thickness in the thinnest corneal zone, with a 52 µm threshold value for discriminating form fruste keratoconic corneas from normal corneas. CONCLUSIONS: The epithelial thickness in the thinnest corneal zone and its location provided by the OCT epithelial mapping might be useful for the early diagnosis of form fruste keratoconus. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Fourier-domain optical coherence tomography imaging in corneal epithelial basement membrane dystrophy: a structural analysis.

PURPOSE: To investigate the features of corneal epithelial basement membrane dystrophy using spectral-domain optical coherence tomography (SD OCT) and to examine the reliability of SD OCT in distinguishing epithelial basement membrane dystrophy from the normal cornea. DESIGN: Diagnostic test study. METHODS: Forty-five individuals with epithelial basement membrane dystrophy and 45 age- and sex-matched controls with normal corneas were examined, and SD OCT scans of their corneas were performed. In vivo confocal microscopy was performed to confirm or rule out the diagnosis of epithelial basement membrane dystrophy. The structural corneal changes occurring in eyes with epithelial basement membrane dystrophy based on SD OCT findings were described. RESULTS: Epithelial abnormalities were observed in 86 of 87 eyes with epithelial basement membrane dystrophy (45 patients) on SD OCT scans. The 2 main features were the presence of an irregular and thickened epithelial basement membrane duplicating or insinuating into the corneal epithelium layer, or both, and the presence of hyperreflective dots. In some cases, we detected hyporeflective spaces between the corneal epithelial layer and the Bowman layer similar to a corneal epithelial detachment. This corneal epithelial detachment sometimes was associated with a cleavage with a stair-step appearance within the corneal epithelial layer. We found a perfect correlation between in vivo confocal microscopy and SD OCT findings in the diagnosis of epithelial basement membrane dystrophy (κ = 0.98). CONCLUSIONS: SD OCT provides an accurate assessment of the structural changes occurring in eyes with epithelial basement membrane dystrophy. These changes, visible on SD OCT scans, are easily detectable and permit an accurate diagnosis, especially in patients with no biomicroscopically visible corneal changes.