The lid wiper and muco-cutaneous junction anatomy of the human eyelid margins: an in vivo confocal and histological study

The inner border of the eyelid margin is critically important for ocular surface integrity because it guarantees the thin spread of the tear film. Its exact morphology in the human is still insufficiently known. The histology in serial sections of upper and lower lid margins in whole-mount specimens from 10 human body donors was compared to in vivo confocal microscopy of eight eyes with a Heidelberg retina-tomograph (HRT II) and attached Rostock cornea module. Behind the posterior margin of the Meibomian orifices, the cornified epidermis stopped abruptly and was replaced by a continuous layer of para-keratinized (pk) cells followed by discontinuous pk cells. The pk cells covered the muco-cutaneous junction (MCJ), the surface of which corresponded to the line of Marx (0.2-0.3 mm wide). Then a stratified epithelium with a conjunctival structure of cuboidal cells, some pk cells, and goblet cells formed an epithelial elevation of typically about 100 μm initial thickness (lid wiper). This continued for 0.3-1.5 mm and formed a slope. The MCJ and lid wiper extended all along the lid margin from nasal to temporal positions in the upper and lower lids. Details of the epithelium and connective tissue were also detectable using the Rostock cornea module. The human inner lid border has distinct zones. Due to its location and morphology, the epithelial lip of the lid wiper appears a suitable structure to spread the tear film and is distinct from the MCJ/line of Marx. Better knowledge of the lid margin appears important for understanding dry eye disease and its morphology can be analysed clinically by in vivo confocal microscopy.     

The nasopalpebral lipoma-coloboma syndrome: A new autosomal dominant dysplasia-malformation syndrome with congenital nasopalpebral lipomas,eyelid colobomas,telecanthus, and maxillary hypoplasia

We describe a new autosomal dominant dysplasia-malformation syndrome from eight affected individuals in three generations of a Venezuelan family. It is characterized by congenital symmetrical upper lid and nasopalpebral lipomas, bilateral symmetrical upper and lower palpebral colobomas located at the junction of the inner and middle thirds of the lids, telecanthus, and maxillary hypoplasia. Affected individuals have a broad forehead, widow's peak, abnormal pattern of eyebrows and eyelashes, and maldevelopment of the lacrimal punctae. Interorbital distance is normal, but interpupillary distance is increased due to divergent strabismus originating from visual interference from inner canthal masses. Persistent epiphora, conjunctival hyperemia, and corneal (and less frequently lens) opacities are a secondary consequence of the defect of the lacrimal punctae and the inability to close the lids completely. The syndrome has complete penetrance and a rather narrow range of expressivity. The primary defect could involve a dysplasia of adipose tissue leading to nasopalpebral and upper lid lipomas during embryogenesis, with the rest of the malformations being secondary to interference of morphogenesis of the mid-upperface developmental field from the lipomatous hamartomas. Alternatively, a central rather than a peripheral mechanism of malformation might be considered, such as defective migration of neural crest cells.     

Corneal Perforation with Preseptal Cellulitis in a Patient with Acute Lymphocytic Leukemia

We report a case of corneal perforation with preseptal cellulitis in a patient with acute lymphocytic leukemia (ALL). A 17-yr-old female patient who was undergoing combination chemotherapy for ALL was referred due to upper lid swelling and pain in the right eye for 2 days. Visual acuity in the right eye was 20/20. Initial examination showed no abnormal findings, other than swelling of the right upper eyelid. Computed tomography showed a finding of preseptal cellulitis. Microbiologic study of bloody and purulent discharge revealed Serratia marcescens. Corneal melting and perforation with iris prolapse were detected in the right eye on the 16th day. Emergent tectonic keratoplasty was performed. Seven months after surgery, visual acuity in the right eye was 20/300, and the corneal graft was stable.     

Apocrine glands in the eyelid of primates contribute to the ocular host defense

Apocrine glands of Moll are regular components of primate eyelids. We studied the distribution and localization of these glands in three different primate species, the common marmoset, the rhesus monkey, and the hamadryas baboon. In addition, we tested the primate glands of Moll with antibodies against antimicrobial proteins, cytoskeletal proteins and the androgen receptor. The glands of Moll differ in abundance and distribution in different monkeys. In the common marmoset, a representative of the New World monkeys, Platyrrhini, the apocrine glands are frequently found at the lid margin and in the overlying epidermis of the lid. In the rhesus monkey and the hamadryas baboon, representatives of Old World monkeys, Catarrhini, apocrine glands are rarer and located predominantly at the margin of the lid. The immunohistochemical analysis indicates the presence of a variety of antimicrobial proteins, e.g. lysozyme, beta-defensin-2, adrenomedullin, lactoferrin, and IgA, in these glands. Interestingly, there are basically no androgen receptors in the nuclei of apocrine glands at the lid margin in all three monkey species. In the common marmoset, however, androgen receptors are found in apocrine glands of the overlying epidermis of the lid. We speculate that the glands of Moll are derived from apocrine glands as found in the skin of the entire body in New World monkeys which developed at the lid margins of higher primates and humans into specialized glands secreting agents of host defense in the eye.     

Distichiasis

Distichiasis is a rare congenital or acquired eyelid anomaly in which an accessory row of eyelashes arises from the openings of meibomian glands or near them. The abnormal cilia are posterior to the normal row of cilia and may abrade the eye causing ocular irritation and corneal damage. We describe a 9-year-old Caucasian girl with bilateral and symmetric distichiasis. This condition was treated with lid splitting followed by cryotherapy to the posterior lid lamella. The technique has been used in four eyelids with congenital distichiasis, with very good results.     

Human eye movements associated with blinks and prolonged eyelid closure

Eye movements associated with eyelid closure were recorded in human subjects with search coils, embedded in self-adhering scleral annuli, in a magnetic field. In contrast to classical notions, voluntary as well as reflex blinks were consistently accompanied by transient downward and nasalward movements of both eyes with amplitudes 1-5 degrees. These eye movements had a shorter duration than the upper lid movements, and the shapes of the spatial trajectories of eye and lid movements were not similar. The trajectory of the eye movements was only modestly affected by gaze eccentricities up to 15 degrees; there was a tendency for the downward component to be enhanced by looking upward, and vice versa. Restraining of the lids of one eye in the open or closed position did not significantly alter the eye movements during (attempted) blinks. Velocity-amplitude-duration relations of the down- and upward components were similar for the same eye before and after closure and for the closed eye and the contralateral unrestrained eye. The velocity-amplitude-duration characteristics of saccades were also unaffected by prolonged closure of the lids of one eye. Prolonged, voluntary closure of the lids was followed by a slow, tonic ocular deviation, which was consistently upward in half of the subjects and consistently downward in the other half. Additional horizontal components were highly variable even within subjects. In one subject the downward deviation was converted into upward deviation when lid closure was mechanically impeded. We conclude that elevation of the eye ball (Bell's phenomenon) does not occur during short blinks and only in about half of the subjects during voluntary unrestrained prolonged lid closure. Our evidence does not support the possibility that the transient eye movements during blinks are caused primarily by a mechanical interaction between the lids and the eye (or the scleral annulus). More likely, they are a secondary effect of an active cocontraction of extraocular muscles that primarily results in retraction of the eye.     

Experimental and morphological as well as physical and chemical interaction of laser radiation of a close infrared range with the fibrous eye membrane

Experimental-and-morphological as well as physical-and-chemical changes occurring in the eye fibrous coat tissues, i.e. the cornea and sclera, at non-ablation impact of fiber laser radiation (Er-glass) with a wavelength of 1.56 mcm were analyzed. Necrobiotic or necrotic changes occur in the tissues with regard for laser radiation capacity and impact duration; subsequently, the regenerative process involving a retraction of the sclera and a flattening of the cornea takes place in the end. When the cornea is heated by fiber laser radiation with a minimally possible intensity (up to 0.3 Wt), a temporary weakening is observed in the corneal rigidity. Should it be accompanied by a simultaneous occurrence of retraction forces coming from the sclera (at its coagulation), it can be used to change, in the clinical controllable mode, the corneal curvature radius.     

Accessory levator muscle of the upper eyelid: Case report and review of the literature

The authors describe a supernumerary muscle in each orbit of an elderly male subject. There appear to be no previous reports of this muscle; most reports of anomalies of extraocular muscles describe hypoplasia or aplasia. Thirty-five formalin-fixed cadavers assigned to medical students for dissection were studied. The orbits were dissected by a superior approach which involved removal of the orbital plate of the frontal bone and the superior orbital margin. A supernumerary extraocular muscle was seen in each orbit of one cadaver, located between the superior oblique and levator palpebrae superioris muscles. It originated on the inferior surface of the lesser wing of sphenoid bone and was inserted into the skin of the medial one-third of the upper eyelid. It was innervated by a branch from the superior division of the oculomotor nerve. The insertion of the muscle into the upper eyelid produced a crease running obliquely upwards and medially, from the junction of the medial one-third and lateral two-thirds of the lid margin, towards the medial part of the superior orbital fold. The authors suggest the name levator palpebrae superioris accessorius for this muscle in view of its topography and action as tested in the cadaver. The significance of the findings is discussed and the literature on the development of the muscles supplied by the oculomotor nerve is reviewed. Clin. Anat. 11:410–416, 1998. © 1998 Wiley-Liss, Inc.     

不同剂型排龈材料对牙龈组织损伤程度的比较

背景：排龈有利于印模准确记录预备体边缘的位置和形态,从而提高固定修复体牙龈边缘的适合性,以确保修复体的成功和长期稳定性。 目的：观察应用排龈线和排龈膏后大鼠牙龈组织的损伤程度。 方法：实验纳入65只Wistar大鼠,分别应用排龈线或排龈膏对大鼠进行排龈处理,以不进行排龈处理的大鼠作为对照。分别在排龈后30 min,1,2,4,7,12 d采集大鼠牙龈组织进行观察。 结果与结论：病理学观察发现,排龈线与排龈膏均导致牙龈组织损伤,并产生炎症反应。排龈线组牙龈炎症反应较排龈膏组重,但排龈12 d后两组牙龈均恢复正常的组织学形态。说明两种排龈剂型都是安全可靠的,但排龈膏对牙龈组织的损伤程度要轻于排龈线,生物学效应更佳。     

Blinking and associated eye movements in humans, guinea pigs, and rabbits

Recordings of upper eyelid movements in humans, guinea pigs, and rabbits demonstrated that all three species displayed qualitatively similar patterns of eyelid movement. The relation between amplitude, duration, and maximum velocity in rabbits and humans was nearly identical. Guinea pig blinks were faster than those of rabbit and man. Electromyographic (EMG) recordings in humans demonstrated that the orbicularis oculis muscle participated in downward movement of the upper eyelid during blinks and eyelid closure but did not participate actively in the downward lid movement occurring with gaze changes. When looking straight ahead, the estimated stiffness and viscosity of the upper eyelid were 10 g/mm and 0.38 g X s X mm-1 for humans and 1.17 g/mm and 0.062 g X s X mm-1 for rabbits. Upward and abducting rotations of the eye accompanied blinks in rabbits and guinea pigs. Simultaneously, the eyeball retracted (translational movement) into the orbit. These translational and rotational eye movements resulted from contraction of the retractor bulbi muscle and cocontraction of antagonistic extraocular muscles. The data suggested that humans also retracted the eye during voluntary blinks. The retraction produced a rotation of the eye toward a "primary position" rather than a rotation in one specific direction. The relationship between the maximum velocity, duration, and amplitude of the down phase of a blink may be expressed as a single equation, maximum velocity = c X average velocity, where c is a constant. The same relationship, with a similar value for c, also describes saccadic eye movements and rapid skeletal movements. This implies that all three movements employ comparable neural mechanisms.     

Different forms of blinks and their two-stage control

Summary The purpose of this paper is to examine blink kinematics and the neural basis of blinks evoked reflexively by different kinds of stimuli. The kinematics of the upper lid movement and the electromyographic response of lid muscles levator palpebrae and orbicularis oculi were recorded in the rabbit during trigeminally and visually-evoked blinks. We find that there is a basic, kinematic difference between blinks. A blink in response to an airpuff is more rapidly accomplished and achieves a higher velocity than does an equal amplitude blink in response to a flash of light. The two forms of the reflex blink result from differences in the nature and timing of activity in antagonistic lid muscle motoneurons. Nevertheless, most characteristics of blink neural control are common to both reflex blinks. Most importantly, it appears that blinks are produced by two-stage neural control, an early component that is preprogrammed and a late component that is under stimulus control.     

Association of diabetes, lash loss, and Staphylococcus aureus with infestation of eyelids by Demodex folliculorum (Acari: Demodicidae)

Six eyelashes, three from the upper lid and three from the lower lid, were epilated from 256 subjects and examined for Demodex. D. folliculorum (Simon) was found in 16% of the subjects. Mites were more abundant in older persons and in persons with diabetes. Mites also were associated with a scarcity of lashes in the lower lid. Hierarchical log-linear analysis showed that the associations of greater mite abundance with diabetes and with madarosis were independent of age. The 43 persons from whose lid margins Staphylococcus aureus was cultured seemed to have been more likely to have two or more mites than those without S. aureus (11.6 versus 5.2%), although this difference fell short of statistical significance (P = 0.125).     

Lid-eye coordination during vertical gaze changes in man and monkey

1. To investigate the coordination between the upper lid and the eye during vertical gaze changes, the movements of the lid and the eye were measured by the electromagnetic search-coil technique in three humans and two monkeys. 2. In both man and monkey, there was a close correspondence between the metrics of the lid movement and those of the concomitant eye movement during vertical fixation, smooth pursuit, and saccades. 3. During steady fixation, the eye and lid assumed essentially equal average positions; however, in man the lid would often undergo small idiosyncratic movements of up to 5 degrees when the eye was completely stationary. 4. During sinusoidal smooth pursuit between 0.2 and 1.0 Hz, the gain and phase shift of eye and lid movements were remarkably similar. The smaller gain and larger phase lag for downward smooth pursuit eye movements was mirrored in a similar reduced gain and increased phase lag for downward lid movements. 5. The time course of vertical lid movements associated with saccades was generally a faithful replica of the time course of the concomitant saccade; the similarity was especially impressive when the details of the velocity profiles were compared. Consequently, lid movements associated with vertical eye saccades are called lid saccades. 6. On average, lid saccades start some 5 ms later than the concomitant eye saccades but reach peak velocity at about the same time as the eye saccade. Concurrent lid and eye saccades in the downward direction have similar amplitudes and velocities. Lid saccades in the upward direction are often smaller and slower than the concomitant eye saccades. The relation of peak velocity versus amplitude and of duration versus amplitude are similar for lid and eye saccades. 7. To investigate the neural signal responsible for lid saccades, isometric tension and EMG activity were recorded from the lids of the two authors. 8. The isometric tensions during upward lid saccades exceeded the tensions required to hold the lid in its final position.(ABSTRACT TRUNCATED AT 400 WORDS)     

The hemangioma-sternum bifidum malformation syndrome. Report of a patient

We present a male patient with a facial haemangioma extending from the lower left lid to the malar region and the upper left lip. The patient also presents a 1 cm round cutaneous notch on the upper third of the sternum. There are not other physical anomalies. The characteristics of the clinical picture suggest the diagnosis of sternal cleft-haemangiomas malformative spectrum (OMIM 140850).     

Further clinical and sensorial delineation of Schinzel-Giedion syndrome: report of two cases

Schinzel-Giedion syndrome is a rare multiple congenital malformation syndrome defined by an evocative midfacial retraction, kidney and urinary malformations and multiple skeletal abnormalities associated to a recently described neurodegenerative process. Two children with SGS are reported with identical clinical findings: megacalycosis, progressive neurodegeneration with infantile spasms and hypsarrhymtic activity. Ocular investigations revealed alacrimia and corneal hypoesthesia. Computed tomography of the temporal bone showed a tuning-fork malformation of the stapes for both children. These features may contribute to further delineation of SGS as additional clinical criteria.     

Clinical and immunological responses in ocular demodecosis

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.     

Immunomorphologic studies of mast cell heterogeneity, location, and distribution in the rat conjunctiva

Mast cells are crucial components of immediate and some delayed-type hypersensitivity reactions. They play a pivotal role in allergic conjunctivitis and other immunoinflammatory disorders of the ocular surface, yet little is known of their distribution and heterogeneity in the conjunctiva of potential animal models, such as the rat. In this study, mast cell types were investigated in histologic sections and corneal-conjunctival-lid whole mounts by using toluidine blue, alcian blue–safranin, and immunohistochemical staining methods (anti-rat mast cell proteinase [RMCP] antibodies). Quantitative analyses were performed on corneal-conjunctival-lid whole mounts by using the optical dissector procedure to obtain the density of mast cells per unit volume in different regions of the conjunctiva. Single and double immunohistochemical analyses revealed that the mast cells in the conjunctiva of the limbus, fornices, and lid margin were strongly RMCP I⁺, suggesting that they were of the connective tissue phenotype. Mast cells containing the mucosal mast cell proteinase RMCP II were not present in the normal conjunctiva. Histochemical analysis revealed that the maturity of the connective tissue mast cells, as assessed by the presence or absence of safranin (heparin)-positive granules in their cytoplasm varied in different regions. In the lid margin 60% to 78% of the mast cells were solely alcian blue–positive, whereas in the fornices 68% to 78% were safranin-positive. In the limbus the predominant type of mast cell was either safranin-positive or contained mixed granules. Mast cell densities were greatest close to the lid margin (10,000 to 12,000 cells/mm³), followed by the limbus (3400 to 4800 cells/mm³) and were rare in the remainder of the conjunctiva (500 to 1000 cells/mm³), with the exception of the region around the nictitating membrane. This study of rat conjunctival mast cells provides essential baseline data for future studies of the role of mast cells in models of allergic conjunctivitis. (J ALLERGY CLIN IMMUNOL 1996;97:1375-86.)     

Changes to the ocular biota with time in extended- and daily-wear disposable contact lens use.

Gram-negative bacteria may play a role in the etiology of certain soft contact lens (SCL)-related diseases. Contact lens (CL) wear may modify the normal ocular biota, providing a more favorable environment for potential pathogens. This study reports temporal changes in ocular biota in daily-wear (DW) and extended-wear (EW) disposable SCL use in experienced and neophyte wearers. Lid margin and bulbar conjunctival biota were sampled prior to CL fitting in 26 previous DW SCL users, 18 previous EW SCL users, and 26 neophytes. Wearers were fitted with an etafilcon A CL in one eye and a polymacon CL in the fellow eye. Lenses were worn on a daily basis by the 26 previous DW SCL wearers and on an EW basis by the remaining 44 subjects. The ocular biota was further sampled after 1, 3, 6, 9, and 12 months of wear. The ocular biota consisted of coagulase-negative staphylococci, Corynebacterium spp., Micrococcus spp., and Propionibacterium spp. Potential pathogens were rarely isolated at baseline. No significant trend of increasing ocular colonization was shown for extended CL wear. Lid and conjunctival colonization increased with DW SCL use (P < 0.001), although this increase occurred for nonpathogenic species only. Fewer potential pathogens were isolated from DW SCL than from EW SCL users (P < 0.05). The lid margin consistently showed greater colonization than the conjunctiva and may be a source of potential pathogens during CL wear. Hydrogel CL wear appears to modify the ocular biota. An increased number of commensal organisms were present in DW SCL use. EW SCL use altered the spectrum of organisms isolated. These alterations may suppress the normal ocular defense mechanisms and may be relevant in the pathogenesis of CL-related disease.     

Local thermal injury elicits immediate dynamic behavioural responses by corneal Langerhans cells

Langerhans cells (LCs) represent a special subset of immature dendritic cells (DCs) that reside in epithelial tissues at the environmental interfaces. Although dynamic interactions of mature DCs with T cells have been visualized in lymph nodes, the cellular behaviours linked with the surveillance of tissues for pathogenic signals, an important function of immature DCs, remain unknown. To visualize LCs in situ, bone marrow cells from C57BL/6 mice expressing the enhanced green fluorescent protein (EGFP) transgene were transplanted into syngeneic wild-type recipients. Motile activities of EGFP(+) corneal LCs in intact organ cultures were then recorded by time lapse two-photon microscopy. At baseline, corneal LCs exhibited a unique motion, termed dendrite surveillance extension and retraction cycling habitude (dSEARCH), characterized by rhythmic extension and retraction of their dendritic processes through intercellular spaces between epithelial cells. Upon pinpoint injury produced by infrared laser, LCs showed augmented dSEARCH and amoeba-like lateral movement. Interleukin (IL)-1 receptor antagonist completely abrogated both injury-associated changes, suggesting roles for IL-1. In the absence of injury, exogenous IL-1 caused a transient increase in dSEARCH without provoking lateral migration, whereas tumour necrosis factor-alpha induced both changes. Our results demonstrate rapid cytokine-mediated behavioural responses by LCs to local tissue injury, providing new insights into the biology of LCs.     

Further clinical and sensorial delineation of Schinzel‐Giedion syndrome: Report of two cases

Schinzel‐Giedion syndrome is a rare multiple congenital malformation syndrome defined by an evocative midfacial retraction, kidney and urinary malformations and multiple skeletal abnormalities associated to a recently described neurodegenerative process. Two children with SGS are reported with identical clinical findings: megacalycosis, progressive neurodegeneration with infantile spasms and hypsarrhymtic activity. Ocular investigations revealed alacrimia and corneal hypoesthesia. Computed tomography of the temporal bone showed a tuning‐fork malformation of the stapes for both children. These features may contribute to further delineation of SGS as additional clinical criteria. © 2002 Wiley‐Liss, Inc.