Jack V. Greiner

Giant Papillary Conjunctivitis in Contact Lens Wearers

A syndrome that occurred in both hard and soft contact lens wearers was characterized by increased mucus, itching, decreased lens tolerance, and giant papillae in the upper tarsal conjunctiva. It developed in as few as three weeks with soft lens wearers but also occurred after months or even years of successful wear. The histology was characterized by basophils, eosinophils, and mast cells in the epithelium, and these cells as well as increased numbers of lymphocytes, plasma cells, and polymorphonuclear leukocytes in the stroma. The syndrome may be immunologic in origin with deposits on the lenses as the antigen, and the syndrome may be a major cause of difficulty in wearing contact lenses once they have been successfully fit.

Tear film lipid layer thickness as a function of blinking.

Alterations in the tear film lipid layer as a function of blinking were investigated using a custom-designed specular reflection monitoring system. The tear film lipid layer of 104 subjects under conditions of normal (“baseline”) blinking and “forceful” blinking was quantitated on the basis of specific interference colors. Deliberate, forceful blinking was found to significantly increase the lipid layer thickness (LLT) of the tear film. The magnitude of increase was found to be correlated with the baseline LLT values; individuals with baseline LLT values of 75-150 nm demonstrated a mean increase in LLT of 33 nm following forceful blinking, whereas subjects with baseline LLT values ≤ 60 nm experienced a mean increase of 19 nm. The difference in the magnitude of increase between the groups was highly significant (p=0.0001). The data suggest that, in addition to playing a role in the spreading of lipid across the tear film, the blinking mechanism may be important in the maintenance of the lipid layer by augmenting the expression of lipids from the meibomian glands.

Langerhans Cells of the Ocular Surface

Recent evidence has been collected by several investigators defining a distinct population of dendritic cells (Langerhans cells) of mesenchymal origin residing in the epidermal surfaces of many mammalian species. These cells play a dominant role in the processing of antigens presented through cutaneous surfaces and carry a Class II histocompatability antigen felt to be of central importance in the afferent arm of allograft rejection. They also possess many of the characteristics of macrophages active in the efferent arm of immunologic responses. An equivalent subset of dendritic cells (Langerhans cells) in ocular surface epithelium of the human, mouse rat, and guinea pig has been identified by enzyme histochemistry, immunofluorescence, and electron microscopy. Ocular surface Langerhans cells proliferate in the setting of corneal inflammation (remote and recent) and are depleted by topical and systemic corticosteroids. Ocular surface Langerhans cells may play a central role in ocular contact hypersensitivity, corneal allograft rejection, and ocular surface immune surveillance.

Lid Wiper Epitheliopathy and Dry Eye Symptoms

Objectives. The lid wiper is defined as that portion of the marginal conjunctiva of the upper eyelid that wipes the ocular surface during blinking. The purpose of this study was to investigate whether lid wiper epitheliopathy occurred with patients who reported dry eye symptoms, yet had normal fluorescein breakup time (FBUT) and Schirmer test values and an absence of fluorescein corneal staining. Methods. One hundred patients were divided into two groups based on the presence or absence of dry eye symptoms, as determined with the Standard Patient Evaluation of Eye Dryness questionnaire. Other criteria for admission to both groups were FBUT of 10 seconds or more, Schirmer test value of 10 mm or more, and absence of fluorescein corneal staining. After instillation of fluorescein and rose bengal dyes, the lid wipers of 50 asymptomatic and 50 symptomatic patients were graded for staining from grade 0 (absent) to grade 3 (severe). Results. Of the symptomatic patients, 76% had staining of the lid wiper: 44%, grade 1; 22%, grade 2; and 10%, grade 3. Of the asymptomatic patients, 12% had staining; 8%, grade 1; 4%, grade 2; and 0%, grade 3. The difference in prevalence of lid wiper staining between the symptomatic and asymptomatic groups was significant (P<0.0001). Conclusions. Lid wiper epitheliopathy, diagnosed by staining with fluorescein and rose bengal dyes, is a frequent finding when symptoms of dry eye are experienced in the absence of routine clinical dry eye findings.

Increase in Tear Film Lipid Layer Thickness Following Treatment with Warm Compresses in Patients with Meibomian Gland Dysfunction

Purpose. Warm-compress therapy applied to the skin of the closed eyelids has been recommended as a treatment for meibomian gland dysfunction (MGD). Previous studies have evaluated the effects of warm-compress therapy on tear-film fluorescein break-up time and tear evaporation rate. The purpose of this study was to determine if tear-film lipid layer thickness (TFLLT) was altered following 5, 15, and 30 minutes of warm, moist compress therapy. Methods. Twenty patients with a diagnosis of dry eye associated with MGD and a baseline TFLLT of ≤ 90 nm (baseline difference between experimental and control eyes ≤ 25 nm) were studied. The skin of the closed eyelids of one eye of each subject was treated for a total of 30 minutes with a compress saturated with warm (40.0 ± 2.0°C) water used as a compress; and the skin of the closed eyelids of the contralateral control eye was treated for a total of 30 minutes with a compress saturated with room-temperature (24.0°C ± 1.0°C) water used as a compress. The subjects’ eyes were randomized into experimental and control eyes. TFLLT was measured at the following time points: 5, 15, and 30 minutes during the 30-minute treatment period, and after 5 minutes following the 30-minute treatment period. Results. The mean baseline TFLLT of the experimental eye prior to treatment with a warm, moist compress was 57.8 ± 12.9 (standard error) nm; after 5 minutes of treatment, TFLLT was 105.8 ± 23.7 nm; after 15 minutes of treatment, 117.8 ± 26.4 nm; after 30 minutes of treatment, 121.5 ± 27.1 nm; and after 5 minutes following the 30-minute treatment, 96.0 ± 21.5 nm. The mean baseline TFLLT of the control eye prior to treatment with a room temperature, moist compress was 63.0 ± 14.1 nm; after 5 minutes of treatment, TFLLT was 63.8 ± 14.3 nm; after 15 minutes of treatment, 62.3 ± 13.9 nm; after 30 minutes of treatment, 64.5 ± 14.4 nm; and after 5 minutes following the 30-minute treatment period, 58.5 ± 13.1 nm. Using a paired-data t- test, the results demonstrated a significant increase in mean TFLLT in the experimental eye after 5 minutes (P < 0.001), 15 minutes (P < 0.001), and 30 minutes (P < 0.001) of treatment, and after 5 minutes following the 30-minute treatment period (P < 0.001) when compared to baseline TFLLT. In comparison, there was no significant increase in TFLLT of the control eye after 5 minutes (P = 0.79), 15 minutes (P = 0.77), and 30 minutes (P = 0.81) of treatment, and after 5 minutes following the 30-minute treatment period (P = 0.20) when compared to baseline TFLLT. Conclusions. Warm, moist compress therapy applied to the skin of the closed eyelids increases TFLLT for subjects with MGD by more than 80%, 5 minutes after initiating treatment and an additional 20% after 15 minutes of treatment. This study supports clinical experience and previous reports on warm, moist compress therapy as an effective treatment for meibomian gland dysfunction.

Increase in Tear Film Lipid Layer Thickness Following Treatment of Meibomian Gland Dysfunction

Meibomian gland lipid secretions contribute to the formation of a stable tear film. Meibomian gland dysfunction may result in dry eye symptoms, keratoconjunctivitis (Keith, 1967; McCulley and Sciallis, 1977) and contact lens intolerance (Henriquez and Korb, 1981), presumably due to an inadequate tear film lipid layer secondary to the meibomian gland dysfunction (MGD) itself. The presence of dysfunctional meibomian glands can often be indicated by serrated and inflamed eyelid margins, although in some instances, signs of inflammation may be lacking. In contrast to normal meibomian glands whose orifices open easily and secrete transparent sebum upon gentle expression, the dysfunctional meibomian gland requires forceful digital pressure to elicit expression of sebum, which is generally cloudy in appearance. Frequently, sebum may not be released from dysfunctional meibomian glands even with forceful digital pressure. The present prospective study evaluated whether a program of manual expression of the meibomian glands of patients with a diagnosis of MGD could increase tear film lipid layer thickness by relieving meibomian gland obstruction.

Number of Inflammatory Cells in the Normal Conjunctiva

We counted inflammatory cells per cubic millimeter in both the epithelium and the substantia propria of samples from upper tarsal conjunctiva of 15 normal subjects and from lower forniceal conjunctiva of ten normal subjects. The upper limit of normal for number of cells was nearly 500,000/mm3. Lymphocytes accounted for about 70% of the inflammatory cells. Neutrophils and lymphocytes were almost always present in both the epithelium and the substantia propria. Plasma cells and mast cells were present in the substantia propria of all subjects, but never in the epithelium. Neither eosinophils nor basophils were found in any specimen. We concluded that conjunctiva of the white and quiet eye usually contains heavy infiltrates of inflammatory cells.

Vernal Conjunctivitis and Contact Lens-Associated Giant Papillary Conjunctivitis Compared and Contrasted

We compared quantitative histologic counts of ten subjects with vernal conjunctivitis to counts of 15 subjects with contact lens-associated giant papillary conjunctivitis and to counts of 15 normal subjects. Both vernal conjunctivitis and contact lens-associated giant papillary conjunctivitis subjects had abnormalities of mast cells in the epithelium, and eosinophils and basophils in epithelium and substantia propria. No normal individuals had these abnormalities. An additional 28 subjects with ocular inflammatory conditions had tissue evaluation for abnormalities of mast cells, eosinophils, and basophils. A few eosinophils were found in four subjects. The histologic abnormalities of vernal conjunctivitis are shared by contact lens-associated giant papillary conjunctivitis but not by conjunctival inflammation in general. Vernal conjunctivitis and contact lens-associated giant papillary conjunctivitis may represent different subtypes of a general category of conjunctival abnormality characterized by giant papillae.

A new system, the LipiFlow, for the treatment of meibomian gland dysfunction.

Purpose To evaluate the safety and effectiveness of the LipiFlow System compared to the iHeat Warm Compress (WC) for adults with meibomian gland dysfunction (MGD). Methods This was a non-significant risk, prospective, open-label, randomized, crossover multicenter clinical trial. One hundred thirty-nine subjects were randomized between LipiFlow (n=69) and WC control (n=70). Subjects in the LipiFlow group received a 12-minute LipiFlow treatment and were reexamined at 1 day, 2 weeks and 4 weeks. Control subjects received a 5-minute iHeat treatment with instructions to perform the same treatment daily for 2 weeks. At 2 weeks, they crossed over (LipiFlow Crossover) and received the LipiFlow treatment. Effectiveness parameters: meibomian gland (MG) assessment, tear break-up time (TBUT) and dry eye symptoms. Safety parameters: adverse events, ocular health exam, ocular surface staining, intraocular pressure, visual acuity and discomfort. Results LipiFlow resulted in significant improvement (P < 0.05) in MG secretion at 2 and 4 weeks (mean ± standard deviation at baseline = 6.3 ± 3.5; 2 weeks = 14.3 ± 8.7; 4 weeks = 16.7 ± 8.7); and TBUT at 2 and 4 weeks: (at baseline = 5.5 ± 2.9; 2 weeks = 6.9 ± 5.0; 4 weeks = 7.4 ± 5.5). There was no significant change in MG secretion or TBUT in the control group. LipiFlow resulted in a greater significant reduction in dry eye symptoms than the iHeat WC. The crossover group demonstrated similar significant improvement 2 weeks post-treatment with the LipiFlow. There was no significant difference between groups in the incidence of non-serious, device-related adverse events. Conclusion The LipiFlow System was significantly more effective than iHeat WC. These results support its safety and effectiveness in the treatment of MGD and dry eye symptoms.

Correlation of lipid layer thickness measurements with fluorescein tear film break-up time and Schirmer's test

AbstractPurpose This study correlates measurement of lipid layer thickness (LLT) with two frequently used dry eye tests, fluorescein break-up time (FBUT) and Schirmers test with anaesthesia (STA).Methods Subjects (n=44 eyes) with symptoms of dry eye and positive results for dry eye with either FBUT or STA or both were selected. Quantification of LLT was performed by the observation of colour interference patterns in zones of specular reflection using a custom-designed instrument.Results All correlations among pairs of tests were strong and exhibited a significance of P<0.000: STA with FBUT, Pearsons correlation 0.653; STA with LLT, 0.764; FBUT with LLT, 0.751. When LLT was high, ie ≥120 nm, which occurred in 14 eyes, STA was also elevated in those eyes and FBUT was high in 13 of the 14 eyes. When LLT was low, ie ≤60, which occurred in 22 eyes, STA was below normal in 14 of the 22 eyes, and FBUT was below normal in 15 of the 22 eyes. These clinical observations paralleled the statistical findings computed from the entire data set.Conclusions The correlations demonstrated in this study support the premise (1) that measurement of LLT is a reliable test for the diagnosis of dry eye, and (2) that aqueous deficiency and lipid deficiency, as they apply to dry eye disorders, are not mutually exclusive.