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Advanced diabetic keratopathy includes impaired corneal sensation, reduced tear secretion, conjunctival squamous metaplasia, and goblet cell loss, as well as susceptibility to corneal erosions and ulcerations. It is thought to be a form of generalized diabetic neuropathy. Early diagnosis of nerve fiber degeneration is essential to prevent further damage. We examined the corneal innervation pattern of patients with diabetes mellitus type 1 and 2 of various durations by in vivo confocal microscopy, and correlated our findings to the severity of diabetic retinopathy, corneal sensation, peripheral diabetic neuropathy in the lower limb, and nephropathy. Nerve fiber length (NFL) was significantly different between patients without diabetic retinopathy and controls (p = 0.028). In patients with non-proliferative diabetic retinopathy (NPDR) and patients with proliferative diabetic retinopathy (PDR), nerve fiber parameters including density (NFD), NFL, and corneal nerve branching (NB) showed a difference with increasing significance compared to healthy persons. A history of nephropathy and/or peripheral neuropathy (all p

To analyze the appearance of conjunctival pigmented tumors as seen by in vivo confocal microscopy. Twenty-eight pigmented conjunctival tumors including 6 nevi, 13 acquired melanoses, 7 conjunctival melanomas, and 2 extrascleral growths of uveal melanomas were examined by in vivo confocal microscopy using the Heidelberg Retina Tomograph (HRTII)/Rostock Cornea Modul (RCM). Confocal images were analyzed using predefined criteria by an observer masked to final histological diagnosis and a preliminary diagnosis was established. After excision, histology and immunohistochemistry using antibodies against S-100, Melan-A, HMB-45, Ki-67, CD3, and CD68 were performed in all specimens and compared with in vivo confocal images of the same lesions. Confocal microscopy images confirmed typical histopathological features of conjunctival pigmented tumors. Nest or diffuse collections of medium-sized uniform hyper- or hyperreflective cells in the stroma and stromal cysts lined with a multilayered epithelium were visible in 100% of conjunctival nevi. Small dendritic cells were typically observed in 100% of primary acquired melanoses (PAM) without atypia and in 2 out of 6 nevi. Large networks of hyperreflective dendritic cells were present in 100% of PAM with atypia. Whereas images of PAM without atypia and secondary complexion-associated melanosis showed hyperreflective granules confined to the basal epithelium in 67% of lesions, PAM with atypia presented with hyperreflective granules and patches throughout the epithelium in all cases. Malignant melanomas of the conjunctiva and extrascleral growths of uveal melanomas demonstrated large hyperreflective cells with prominent nuclei and nucleoli. In vivo confocal microscopy showed a sensitivity of 89% and a specificity of 100% to establish the correct diagnosis of conjunctival melanoma compared with histology. High correlations were found between in vivo confocal microscopy using near-infrared laser light and histology in the diagnosis of pigmented conjunctival lesions. In vivo confocal microscopy seems to be a valuable new tool in the differential diagnosis and follow-up of pigmented conjunctival tumors. It does not replace histology, but may assist in performing guided biopsy in tumors suspected clinically and/or with in vivo microscopy. In addition, in vivo confocal microscopy may support the clinical diagnosis of extrascleral involvement in uveal melanoma.

Background Dysfunction of the meibomian glands with inflammation and obstruction has been suggested to be an important factor in the pathogenesis of chronic blepharitis. Few objective tests are, however, available to examine the meibomian glands directly. Patients and methods Nineteen patients with anterior blepharitis, meibomitis, meibomian gland dysfunction or severe keratoconjunctivitis sicca associated with blepharitis as well as 10 patients with normal lid margins were examined with the HRTII/RCM in vivo confocal microscope. Scans of the tear film, the tarsal conjunctiva, the hair follicles and the meibomian glands were analysed by a masked observer. Results Patients with normal lid margins exhibited a minimal round cell infiltrate in the tarsal conjunctival epithelium and largely normal ducts of the meibomian glands lined with a multilayered epithelium as well as normal gland acini. In patients with anterior blepharitis, blepharitis associated with autoimmune peripheral ulcerative keratitis and blepharitis in the context of severe dry eye, confocal microscopy disclosed normal meibomian glands. In 12 patients with blepharitis/meibomitis or meibomian gland dysfunction, profound pathology was visible with dilatation and obstruction of the meibomian gland ducts. In 15 of 19 patients with blepharitis/meibomitis, but not in meibomian gland dysfunction, an intense inflammation was observed in the tarsal conjunctival epithelium and stroma. In one patient, demodex folliculorum was evident in vivo. In patients with normal lid margins as well as in patients with blepharitis, hair follicles appeared within normal limits. Conclusions In vivo confocal microscopy allowed the examination of the tear film, the tarsal conjunctiva, the lid margin including the lash follicles and the meibomian glands. In patients with meibomian gland disease pathological changes could be visualised and documented objectively. The presence of an inflammatory infiltrate permitted us to differentiate between meibomitis and meibomian gland dysfunction. Changes of the lash follicles do not seem to play an important role in blepharitis. Thus, in vivo confocal microscopy represents an objective technique in the classification and follow-up of patients with blepharitis.

To analyze the appearance of normal conjunctiva and conjunctival inflammation by in vivo confocal microscopy.Conjunctiva of 15 normal patients and 21 patients with conjunctivitis including bacterial, papillary, follicular, granulomatous, and cicatrizing disease were analyzed by the Heidelberg retina tomograph (HRTII)/Rostock cornea modul (RCM).Scans of normal bulbar and tarsal conjunctiva corresponded well to the established anatomy except for a prominent, thickened epithelial basement membrane observed by in vivo microscopy. Presumed goblet cells were visible throughout the conjunctival epithelium. Adenoid structures and hair follicles were discernible in the tarsal conjunctiva in vivo. Conjunctival perfusion could be observed directly. Acute and chronic inflammatory cells, conjunctival papillary, and follicular reactions, as well as conjunctival cicatrization, could be discriminated. In a patient with conjunctival granuloma, in vivo confocal microscopy disclosed suture material inside the lesion.Confocal microscopy using near-infrared laser light is a useful new tool in the analysis of conjunctival tissue in vivo. It is a valuable aid in the differential diagnosis of conjunctival inflammation and thus may guide therapeutical decisions.

To analyze filtering blebs after trabeculectomy by means of in vivo confocal microscopy and to correlate the images with clinical bleb appearance and function.In vivo confocal microscopy using the Heidelberg Retina Tomograph/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany) was performed in 53 filtering blebs in 45 patients 6 days to 30 years postoperatively.In vivo confocal microscopic findings significantly correlated with good bleb function included the number of epithelial microcysts (P = .03), a large total stromal cyst area (P = .009), the absence of encapsulated stromal cysts (P = .002), minimal vascularization (P = .05), and the absence of tortuous conjunctival vessels (P = .01). In contrast, a hyperreflective condensed bleb stroma was significantly associated with bleb failure (P.001). Bleb stroma mainly consisting of a rarified collagenlike network was significantly linked to trabeculectomy performed with mitomycin C (P = .001). Epithelial and stromal inflammation were observed at a median of 1 and 4 months after surgery, respectively.In vivo confocal microscopy using the Heidelberg Retina Tomograph/Rostock Cornea Module permits diagnostic imaging of filtering blebs and differentiation between good and insufficient bleb function. Moreover, the postoperative inflammatory reaction can be monitored directly for adapted postoperative anti-inflammatory treatment.