Marshall G. Doane

Interaction of Eyelids and Tears in Corneal Wetting and the Dynamics of the Normal Human Eyeblink

We used a high-speed camera system to study in detail the eyelid motion dynamics of the human eyeblink. Films were made from a hidden location through a one-way mirror. In this manner, normal, unforced blinks were recorded. The descent of the upper eyelid reached its maximum speed at about the time that it crossed the visual axis, generally in the range of 17 to 20 cm/sec, but occasionally reaching a speed of over 40 cm/sec. The motion of the lower eyelid was mostly horizontal, in a nasally directed movement, with a total displacement in the range of 20 to 5 min. A distinction must be made between normal, unforced blinks, and voluntary, forced eyelid motion. In a normal blink, no appreciable upward rotation of the globe is observed. A forced blink or a restraint of motion of the upper eyelid results in a significant demonstration of Bells movement. The globe moves posteriorly up to 1 to 6 mm as the upper eyelid descends, probably caused by eyelid pressure during the closing phase of the blink.

Keratoprosthesis: preoperative prognostic categories.

Purpose. Recent advances aimed at preventing and treating complications after keratoprosthesis surgery have improved prognosis, but it has been suspected that various preoperative diagnoses may carry substantially different postoperative outcomes. This article attempts to clarify the ranking of prognostic categories for patients undergoing keratoprosthesis surgery. Methods. A retrospective review of the outcome in a recent series of 63 patient eyes operated at the Massachusetts Eye and Ear Infirmary between 1990 and 1997 and followed up for a minimum of 21 months. Anatomic retention of the device and the loss of vision caused by complications were recorded. The patients were divided into four categories according to preoperative cause. Results. Anatomically, one keratoprosthesis extruded spontaneously. Another 10 were permanently removed because of complications. Of the 63 eyes, 10 never achieved a visual acuity of at least 20/200 vision because of preexisting retinal or optic nerve damage. The remaining 53 had a visual acuity of 20/200 to 20/20 as follows: Stevens–Johnson syndrome (n = 7), after 2 years: 33%, after 5 years: 0%; chemical burn (n = 17), after 2 years: 64%, after 5 years: 25%; ocular cicatricial pemphigoid (n = 20), after 2 years: 72%, after 5 years: 43%; graft failure in noncicatrizing conditions (dystrophies, degenerations, or bacterial or viral infections) when a repeat graft was expected to have a poor prognosis (n = 19), after 2 years: 83%, after 5 years: 68%. The difference in outcome between the Stevens–Johnson syndrome outcome group and the graft failure group or the ocular cicatricial pemphigoid group was statistically significant. In the group of 53 eyes, visual acuity was restored to 20/200 to 20/20 for a cumulative total of 138 years. Conclusion. Outcome of the keratoprosthesis surgery varied markedly with preoperative diagnosis. Most favorable was graft failures in noncicatrizing conditions, whereas Stevens–Johnson syndrome was the worst. Ocular cicatricial pemphigoid and chemical burns occupied a middle ground. The difference between the groups seemed to correlate with the degree of past preoperative inflammation.

Penetration routes of topically applied eye medications

Tritium-labeled hydrocortisone acetate and pilcarpine hydrochloride solutions were topically applied to the eyes of rabbits. In one group of animals, the drugs were excluded from contact with the cornea by a cylindrical well glued to the eye surface. In another group, the drug solutions were allowed contact with the entire anterior surface of the eye. Total application time in all cases was five minutes, then the eyes were flushed with saline. Samples of aqueous humor, stroma, and iris-ciliary body were taken after five, 20, 35, 65, and 125 minutes and counted in a liquid scintillation counter. With hydrocortisone, up to 70 times more drug reached the stroma when the cornea was exposed; 40 times more reached the iris. Peak stromal levels occurred by 20 minutes, dropping to one third of peak value by two hours. With pilocarpine, about five times more drug reached the iris-ciliary body when corneal access was allowed; the level peaked in about five minutes. These results illustrate the important role of tear film distribution and blinking in delivering remotely applied drugs over the cornea with subsequent entry to interior sites.

Effect of contact lens materials on tear physiology.

Purpose. This study measured evaporation rate, thinning characteristics, and lipid layer changes in the prelens tear film (PLTF) associated with wearing of different soft contact lens materials, in an attempt to determine the biocompatibility of the material with the PLTF. Methods. Twenty habituated contact lens wearers wore five different soft materials in a random order on the left eye at visits separated by at least 24 h. The soft contact lens materials were polymacon (Optima 38), omafilcon A (Proclear Compatibles), phemfilcon A (DuraSoft 2), balafilcon A (PureVision), and etafilcon A (Acuvue). Tear film evaporation rate was measured by a modified Servo Med Evaporimeter and tear thinning time by HirCal grid. Tear film structure, elimination rate, and lens wetting ability were recorded dynamically with a Doane tear film video interferometer and graded according to a new system developed for the study. Baseline measurements were taken of the precorneal tear film before lens insertion, and PLTF was determined 30 min after commencing lens wear. Results. No statistically significant differences were found for any of the baseline (precorneal tear film) data. There was also no significant difference in evaporation rate change (analysis of variance) and in tear thinning time (Friedmann) between the five contact lenses. In the PLTF structure grading, omafilcon A had significantly more stable grades than phemfilcon A (Friedmann, p = 0.0033) and polymacon (p = 0.004). In PLTF observation of tear thinning and elimination rate, there was a significantly slower rate of elimination observed for omafilcon A than phemfilcon A (Friedmann, p = 0.0023) and polymacon (p = 0.0023). There was no significant difference in the overall PLTF wetting ability grading between any of the lenses worn. Conclusion. Generally, all soft contact lens materials significantly and adversely affected tear physiology by increasing the evaporation rate and decreasing tear thinning time. The surface wetting ability of all contact lens materials exhibited no significantly difference irrespective of the special surface treatments. Only in PLTF structure and in PLTF elimination rate were differences found from the conventional low water content materials; omafilcon A was better in PLTF structure and in PLTF elimination.

FABRICATION OF A KERATOPROSTHESIS

For patients with opaque corneas that have a poor prognosis when using regular corneal transplants, a clear plastic “window” in the form of a keratoprosthesis may offer the only hope of usable vision. Various forms of such devices have been used for many years with varying degrees of success. The design, fabrication, and optical testing of two variations of a polymethylmethacrylate (PMMA) keratoprosthesis are described. Type 1 consists of a twin-plate collarbutton-style design that is used in eyes that have sufficient tear fluid production to maintain wetting of the anterior surface of the eye. Type 2 is of a similar design, with an added anterior cylinder that protrudes through a permanently closed eyelid, and is used in end-stage dry eyes.

Some factors influencing outcome after keratoprosthesis surgery.

Eleven patients with severe corneal disease have been operated with a collarbutton-shaped keratoprosthesis and have been followed for 9-36 months. Two of the devices have been removed, but the remainder are securely in place. Six of the patients have benefitted substantially in terms of improved vision. The complications have been reviewed, and some factors for success have been identified. Thus, to keep the keratoprosthesis temporarily buried beneath tissue (conjunctiva or skin), application of collagenase-suppressing medication and reduction of evaporative damage to the wound around the device seem particularly important.

Tear volume in normal eyes and keratoconjunctivitis sicca

Tear volume measurements were made in normal individuals and in patients with keratoconjunctivitis sicca using a fluorescein dilution method. The mean tear volume in normals was found to be 6.5±0.3μl (S.E.M.) with a range of 3.4 to 10.7 μl. In sixteen eyes with keratoconjunctivitis sicca most of the values were moderately decreased with a mean of 4.8±0.4μl and a range of 2.9 to 8.0μl. This decrease seems to manifest itself primarily as a reduction of the tear meniscus. Among the keratoconjunctivitis sicca patients there was no correlation between the values of volume and the results of the Schirmer test or the degree of Rose bengal staining. On the basis of average Schirmer test values for unstimulated tear secretion (“basic secretion”), the tear secretion rate was estimated to range from 0.6 to 1.1μl/min in normals, and from virtually zero to 0.2μl/min in the patients with keratoconjunctivitis sicca. Bei Normalpersonen und Patienten mit Keratoconjunctivitis sicca wurden mit einer Fluoreszeinverdünnungsmethode Tränenvolumenmessungen durchgeführt. Der Mittelwert des Tränenvolumens lag in der Vergleichsgruppe bei 6,5±0,3μl (σx) mit einem Bereich von 3,4–10,7μl. Bei 16 Augen mit Keratoconjunctivitis sicca waren die meisten Werte mäßig erniedrigt mit einem Mittelwert von 4,8±0,4μl und einem Bereich von 2,9–8,0μl. Diese Erniedrigung scheint sich in erster Linie als eine Reduktion des Tränenmeniscus zu manifestieren. Bei den Patienten mit Keratoconjunctivitis sicca bestand keine Beziehung zwischen den Tränenvolumenwerten und den Ergebnissen des Schirmertests oder dem Ausmaß der Bengalrot-Färbung. Auf der Grundlage durchschnittlicher Schirmertestwerte für die nicht stimulierte Tränensekretion („basale Sekretion“) wurde die Tränensekretionsrate geschätzt; sie liegt hiernach beim normalen Auge zwischen 0,6 und 1,1μl/min, beim Patienten mit Keratoconjuctivitis sicca zwischen praktisch Null und 0,2μl/min.

Inputs and Outputs of the Lacrimal system: Review of Production and Evaporative Loss

Meta-analyses were carried out of studies of tear production (by fluorophotometry, tear turnover rate[TTR]) and evaporation (from capture of fluid loss from the eye). TTR was reduced in dry eye relative to normal at 9.26 +/- 5.08%/min (0.54 +/- 0.28 μl/min) vs 16.19 +/- 5.1%/min (1.03 +/- 0.39 μl/min); with values of 7.71 +/- 1.02 %/min (0.4 +/- 0.10 μl/min) in aqueous deficiency dry eye (ADDE) and 11.95 +/- 4.25%/min (0.71 +/- 0.25 l/min) in evaporative dry eye (EDE). Evaporation was increased in dry eye at 21.05 +/- 13.96 x 10(-7)g/cm(2)/s (0.21 +/- 0.13 μl/min) vs 13.57 +/- 6.52 x 10(-7)g/cm(2)/s (0.14 +/- 0.07 μl/min) in normals; with values of 17.91 +/- 10.49 x 10(-7)g/cm(2)/s (0.17 +/- 0.1 μl/min) in ADDE and 25.34 +/- 13.08 x 10(-7)g/cm(2)/s (0.26 +/- 0.16 μl/min) in EDE. Evaporation rate from tear film thinning was also considered, and possible reasons and consequences for the much higher rates thereby reported are discussed. A new statistical approach determined diagnostic efficacy of cut-offs for dry eye derived from the meta-analyses; sensitivities and specifications ranging from 69.5 to 98.6% and 58.7 to 96.8% (TTR) and 45.5 to 61.2% and 79.8 to 90.6% (evaporation). Indices of tear dynamics were reconsidered, and ratios of evaporation and TTR suggest that an increase of between 2 and 3 times may be associated with dry eye.

Abnormalities of the Structure of the Superficial Lipid Layer on the in Vivo Dry-Eye Tear Film

The complexity of the tear film covering the anterior surface of the human cornea has become increasingly evident with recent investigations into its structure and chemical composition. The three-layered structure proposed by Wolff1, perhaps useful as an approximation, is a considerable simplification of reality. While the oily lipid portion of the tear film usually forms a thin layer on the anterior surface of the tear film, as proposed by Wolff, the distribution of other components, such as mucins, appear to be not as well stratified. For instance, there is increasing evidence that a significant portion the mucin component, in highly-hydrated form, is present throughout the aqueous phase as well as being adherent, in a rather thick coating, to the surface of the epithelial layer of the cornea. This mucin coating is much thicker than that proposed by early investigators, at least 1 micron, and perhaps very much greater. Most of this mucin is probably restricted in its ability to freely enter the aqueous phase of the tear film. Thus, the fluid portion of the tear film is now often described as having two layers, rather than three. These consist of the floating lipid phase, secreted primarily by the meibomian glands within the eyelids, and the aqueous phase, a watery solution containing “everything else”, the major components being secreted by the main and accessory lacrimal glands.

Tear Film Interferometry as a Diagnostic Tool for Evaluating Normal and Dry-Eye Tear Film

The technique and method of thin film interferometry is being increasingly employed in the examination of the lipid layer of the in vivo tear film in normal and dry-eye individuals, with and without contact lenses present.1–10 This technique permits determination of the thickness of the superficial lipid layer that floats upon the normal tear film and of the fluid layer that covers the anterior surface of contact lenses. In general, these thickness estimates have been based upon the general hue (color) of the reflected interference patterns. For reasons discussed later, the determination of overall tear film thickness (i.e., from air boundary to corneal surface) is not easily accomplished, as can be verified by the work of Prydal et al.11,12