Cutaneous Permeation of a Percutaneously Applied Glucocorticoid Using Plant-Based Anionic Phospholipids in Hydrogenated Vegetable Oil: A Preliminary Study.

Purpose: It is important that, when corticosteroids are used therapeutically, concentrations be reduced as much as possible to mitigate potential adverse events and side effects. This preliminary study compares the permeation for the delivery of a corticosteroid in a 1% hydrocortisone-supplemented topical cream containing anionic polar phospholipids (APP) in hydrogenated vegetable oil (triglyceride) versus a market-leading 1% hydrocortisone in a mineral hydrocarbon-based skin cream. Methods: Using the Franz diffusion cell method with cadaveric skin, the permeation of a 1% hydrocortisone-supplemented cream containing APP (test preparation) was compared with a commercially available 1% hydrocortisone cream (control preparation). The principal APP in the test preparation were phosphatidylinositol, phosphatidylserine and phosphatidylglycerol. Permeation was determined at 4 and 8 h time intervals. Results: The permeation values for the 1% hydrocortisone supplemental APP cream (test preparation) were comparatively very high 1180 ng/cm2 at 4 h and 2173 ng/cm2 at 8 h, in contrast to the 1% hydrocortisone cream (control preparation) values of 13 ng/cm2 at 4 h and 98 ng/cm2 at 8 h. Permeation of skin cream increased significantly from 0 to 4 and 8 h, when comparing the APP test preparation with the control preparation (p < 0.001). This translates, respectively, into the 90-fold greater and a 20-fold greater penetration of the test preparation APP cream over the 1% hydrocortisone cream at 4 h and 8 h time points. Conclusions: This preliminary study demonstrates the enhanced permeation of 1% hydrocortisone when applied topically to the skin in an APP skin cream vehicle. This enhanced permeation suggests the potential use of APP technology to deliver therapeutically effective hydrocortisone treatment to the skin at markedly reduced concentrations of steroid. As such, APP technology may offer an improved approach to the treatment of dermatoses associated with inflammatory diseases and conditions requiring prolonged topical corticosteroid therapy.

Corneal absorption of glycerylphosphorylcholine.

This study documents the absorption of glycerylphosphorylcholine (GPC) into corneas ex vivo. Corneas in quadruplicate were incubated in preservation medium containing 30 mM GPC, which is used as a reference marker. The GPC reference marker is used to calibrate 31P nuclear magnetic resonance (NMR) spectral chemical-shift positions for identification of phosphatic metabolites and to calculate intracorneal pH in intact tissues ex vivo. Following baseline NMR ex vivo analysis, corneas were stored in eye bank chambers in preservation medium containing 30 mM GPC at 4 °C overnight for 8 h. After returning to room temperature, NMR analysis was repeated on the same corneas in fresh GPC-free preservation medium. NMR analysis also was performed on the 30 mM GPC preservation medium alone from the eye bank chambers for detection of the GPC signal. The elevated GPC signal unexpectedly persisted in corneas incubated at 4 °C overnight even though GPC was not present in the fresh GPC-free preservation medium. In fact, the concentration of GPC in the intact cornea was many times higher than that found in the cornea endogenously. The levels of phosphatic metabolites and the energy modulus, after subtracting the spectral contribution of the 30 mM exogenous GPC, as well as the intracorneal pH remained unchanged from pre-refrigeration analyses. Corneas also retained transparency through the time-course of this study irrespective of temperature or change in temperature. The GPC signal in the NMR analysis of the preservation medium from the eye bank chambers was nearly undetectable. GPC was unexpectedly absorbed into the corneal tissue without detectable metabolic or physical toxicity. The intracorneal uptake of GPC at reduced temperatures parallels the increase in GPC that occurs naturally in muscle tissue in animals during wintering periods and the very high concentration of GPC in sperm, a cryogenically compatible cell, suggestive of a potential role for GPC in cryopreservation.

Corneal Cryopreservation Using Glycerylphosphorylcholine-Enriched Medium.

PURPOSE: To determine the effects of prolonged cryopreservation at subzero-degree temperatures on corneal transparency and histology after treatment with preservation medium containing the phosphodiester glycerylphosphorylcholine (GPC). METHODS: Rabbit corneas (n = 30) were immersed for 3 hours in K-Sol preservation medium containing 30 mM GPC. Three groups with 6 corneas each were refrigerated at -8°C for 2 weeks and liquid nitrogen temperature for 2 and 6 weeks, respectively. Two groups with 6 corneas each immersed in K-Sol preservation medium only were refrigerated at -8°C for 2 weeks and liquid nitrogen temperature for 6 weeks, respectively. Postthawing corneal transparency was measured on a grading scale after which corneas were prepared for and analyzed by light and transmission electron microscopy. RESULTS: All 3 groups of corneas preserved with GPC maintained a greater degree of corneal transparency compared with corneas preserved without GPC. The number of corneas retaining epithelial and endothelial layers increased in all groups where corneas were preserved in medium containing GPC, in contrast to corneas preserved in medium without GPC. Cytoplasmic vacuolization or nuclear damage was greater in corneas preserved without GPC. Similar findings were found in corneas stored at -8°C and liquid nitrogen temperatures. CONCLUSIONS: This study demonstrates a cryoprotective effect of corneas preserved in K-Sol containing the phosphodiester GPC at subzero-degree temperatures. In corneas immersed in preservation medium containing GPC, a higher degree of transparency is maintained and a lesser degree of histopathologic changes is observed with storage at both -8°C and in liquid nitrogen.

Clinically Relevant Immune-Cellular Metrics of Inflammation in Meibomian Gland Dysfunction.

Purpose: To determine the reliability and clinical relevance of in vivo confocal microscopy (IVCM)-based immune-cellular metrics of palpebral conjunctival inflammation in meibomian gland dysfunction (MGD). Methods: Sixteen MGD patients and 13 reference controls included in this cross-sectional, retrospective study, had an ocular surface exam, symptom assessment (Ocular Surface Disease Index questionnaire [OSDI]), and palpebral conjunctival IVCM imaging. Bland-Altman analyses, intraclass correlation coefficient (ICCa), Lin's concordance correlation coefficient (ρc), receiver operating characteristic (ROC) analyses, and correlations were performed. Clinical outcome measures were symptom severity (OSDI scores), tear break-up time (TBUT), and corneal fluorescein staining (CFS grade). Results: Compared to controls, patients with MGD had variable symptom severity (average OSDI score: 48.3 ± 7.6, P = 0.0008, range: 8.3-85.42), shorter TBUT (6.8 ± 0.9 seconds, P = 0.002), comparable corneal staining (0.31 ± 0.19, P = 0.20), and greater conjunctival inflammation (epithelial immune cells [EIC]: 477.8 ± 54.2 vs. 123.3 ± 17.2 cells/mm2, P < 0.0001; intraglandular immune cells [IGIC]: 41.9 ± 3.3% vs. 20.33 ± 7.3%, P < 0.01). Immune-cellular metrics had high inter- and intraobserver agreement (ρc: 0.86-0.94; ICCa and Cronbach's α: 0.85-0.97, P < 0.0001). EIC correlated positively with OSDI (rs: 0.49, P = 0.03), while both EIC and IGIC correlated inversely with TBUT (rs: -0.47, -0.45, P < 0.05), and had high accuracy in detecting inflammation (ROC area under the curve [AUC]: 0.97 and 0.89, P ≤ 0.001). Conclusions: EIC and IGIC are increased in highly symptomatic patients with MGD that have minimal corneal staining, and correlate with symptoms and clinical signs. EIC and IGIC may provide reliable and clinically relevant metrics of inflammation.

TFOS DEWS II Management and Therapy Report.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

A Comparative Study Between an Oil-in-Water Emulsion and Nonlipid Eye Drops Used for Rewetting Contact Lenses.

OBJECTIVES: The purpose of this study was to determine the clinical impact of using SYSTANE BALANCE Lubricant Eye Drops (Alcon, Fort Worth, TX), an oil-in-water emulsion, as a rewetting eye drop in symptomatic contact lens wearers. METHODS: Subjects who had previously experienced contact lens discomfort (CLD), with a mean lens wearing history of 18.6±12.8 years, were randomly assigned to use a Test (SYSTANE BALANCE Lubricant Eye Drops; n=76) or control (habitual nonlipid contact lens rewetting eye drop; n=30) drop over their contact lenses within 5 min of lens insertion and then subsequently at 2 hr intervals up to a maximum of 4 drops per eye daily for a 1-month period. Assessments of subjective comfort, comfortable wearing time, lid wiper epitheliopathy (LWE), and corneal staining were conducted at baseline and after 1 month, after 6 hr of lens wear. RESULTS: Comfort, wearing time, LWE, and corneal staining all showed statistically significant improvements in the test group using SYSTANE BALANCE Lubricant Eye Drops at the 1-month visit compared with baseline data (all P<0.01) and compared with the control group at the 1-month visit (P<0.01, P=0.01, P<0.01, and P=0.03, respectively). CONCLUSIONS: The use of SYSTANE BALANCE Lubricant Eye Drops as a rewetting drop in a group of wearers who experienced symptoms of CLD improved subjective comfort scores, increased comfortable wearing time, and reduced signs of LWE and corneal staining, when compared with the use of non-lipid-containing contact lens rewetting eye drops.

All Warm Compresses Are Not Equally Efficacious.

PURPOSE: To investigate which warm compress (WC) methods used in a small case series are the most effective in providing heat to the inner eyelids for the supplemental treatment of meibomian gland dysfunction. METHODS: Inclusion criteria included the following: 18 years or older and willingness to participate in the study, no current ocular inflammation/disease, and no ocular surgery within the last 6 months. Five patients were fully consented and enrolled. Various forms of contact and noncontact WC heating methods (dry, wet/moist, and chemically activated dry heat) were tested. A paired contralateral design was used; each subject had a heated test eye and an unheated control eye. For both test and control eyes, the temperature of the external upper, external lower, and internal lower lids was measured at baseline and every 2 minutes for 10 minutes during application. Each participant underwent each of the eight treatments under study. Microwaved compresses were heated to 47 ± 1.0°C; two compresses were self-heating and thus not under investigator control. RESULTS: The mean (± SD) age of the patients was 42.2 (± 20.3) years. Out of the eight methods tested, the bundled wet/moist towel method was the only compress that elevated the temperature of all three lid surfaces (external upper, external lower, and internal lower lids) to 40°C or higher. The chemically activated EyeGiene, MGDRx EyeBag, and MediBeads compresses resulted in the lowest temperature increase at the inner palpebral surface. CONCLUSIONS: The Bundle method, although the most labor intensive, increased lid temperatures above therapeutic levels, as reported in the literature, for all measured sections during the WC application. As such, this method of WC application can be recommended for supplemental at-home therapy for meibomian gland dysfunction and any condition requiring that therapeutic heat of 40°C be administered to the meibomian glands.

"Dry Eye" Is the Wrong Diagnosis for Millions.

The clinical perspective that dry eye is, at best, an incomplete diagnosis and the benefit of an etiology-based approach to dry eye are presented. To provide context for this perspective, the historical and current definition of dry eye is reviewed. The paradigm shift introduced by the Meibomian Gland Dysfunction (MGD) Workshop, that MGD is likely the leading cause of dry eye, is discussed in combination with the advancements in the diagnosis and treatment of MGD. To facilitate discussion on the benefit of an etiology-based approach, a retrospective observational analysis was performed on deidentified data from eligible, fully consented, refractory dry eye patients, where conventional sequelae-based dry eye treatment had failed. In this refractory population, the diagnosis of MGD, which directed treatment to evacuating gland obstructions and rehabilitating gland function, was successful. The clinical perspective that "dry eye" is the wrong diagnosis for millions is provocative. However, the MGD-first approach has the potential to revolutionize the timing of diagnosis and the choice of frontline therapy in most patients with dry eye. Additionally, the ability to screen for MGD in its earliest stages, during routine care, expands the scope of clinical practice to include early intervention. For most patients, we are no longer constrained to delay diagnosis until the tear film has decompensated and the cascade of inflammation has ensued. We do not have to wait for our patients to tell us there is a problem.

Treatment for meibomian gland dysfunction and dry eye symptoms with a single-dose vectored thermal pulsation: a review.

PURPOSE OF REVIEW: Meibomian gland dysfunction (MGD) is understood to be a highly prevalent, chronic progressive disease and the leading cause of dry eye. All available published peer-reviewed results of the novel vectored thermal pulsation therapy for patients with MGD are investigated. RECENT FINDINGS: The PubMed and meeting abstract search revealed a total of 31 peer-reviewed reports on vectored thermal pulsation therapy at the time of the search (eight manuscripts and 23 meeting abstracts). All manuscripts evidence a significant increase in meibomian gland function (∼3×) and symptom improvement post a single 12-min treatment. Additional reported objective measures such as osmolarity, tear break-up time, or lipid layer thickness also increased as a result of the therapy; however, not all findings were statistically significant. The randomized controlled studies evidence sustained gland function and symptom relief lasting out to 12 months. The uncontrolled case series evidence significantly longer duration of effect. SUMMARY: A single 12 minute vectored thermal pulsation treatment allows for reducing dry eye symptoms, improving meibomian gland function and other correlates of the ocular surface health.

Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on meibomian gland functionality in patients with lipid deficient/evaporative dry eye.

PURPOSE: The aim of this study was to assess the efficacy of using a combination treatment approach consisting of lipid emulsion eye drops, eyelid cleansing wipes, and omega-3 vitamin supplements compared with warm compresses in improving meibomian gland functionality in patients with lipid-deficient/evaporative dry eye disease (LDDE). METHODS: This single-center, open-label, investigator-masked, randomized study enrolled patients aged ≥18 years, clinically diagnosed with LDDE defined as having ≤6 functional meibomian glands [meibomian gland yielding liquid secretion (MGYLS)] and positive for dry eye symptoms at screening. Patients were randomized to receive either the combination treatment (lipid emulsion eye drops, omega-3 supplements, and lid hygiene with eyelid wipes) or to apply warm, wet compresses once daily, 8 minutes per day, for 3 months. Meibomian gland functionality (number of MGYLS; primary outcome) and patient-reported subjective assessments (SPEED and OSDI questionnaires; secondary outcomes) were evaluated. Adverse events (AEs) and visual acuity were assessed as safety endpoints. RESULTS: Mean patient age was 41.7 years (n = 26; n = 13 per group). Mean ± SD number of MGYLS was not statistically significantly different between groups at baseline (combination treatment, 3.5 ± 1.5; warm compresses, 4.2 ± 1.4, P > 0.5), and was significantly greater with combination treatment versus warm compresses after 3 months of treatment (9.3 ± 2.7 vs. 4.7 ± 2.3; P = 0.006). Dry eye symptoms were significantly improved in both groups at all follow-up visits. Two AEs unrelated to treatment were reported; the BCVA was unchanged from baseline in both groups. CONCLUSIONS: The combination treatment regimen resulted in significant improvement in meibomian gland functionality and dry eye symptoms. No safety issues were observed.

A new model of central lid margin apposition and tear film mixing in spontaneous blinking.

PURPOSE: To investigate tear film spreading and central lid position in spontaneous blinks and to propose a model of the central lid position of the closed eye in such blinks. METHOD: In vivo: lid margin position and geometry of 15 subjects (9 female; median age=45 years) were evaluated by high-speed video and slit-lamp microscope video in consecutive spontaneous blinks. Upper lid (UL) tear meniscus (TM) depth was observed in the open and almost closed eye. Eyelid geometry, position and UL TM depth were analysed by Image-J Software. Lid margin thicknesses were measured with a Scheimpflug camera. In vitro: tear film spreading and lipid layer formation were simulated on a lubricated glass plate and videoed by high-speed camera (JVC, GZ-GX1BE, Japan). RESULTS: In vivo: the median central lid margin thickness was not significantly (p=0.258) different between UL (1.8mm) and LL (1.7mm) in the opened eye. During blinking, UL remained perpendicular to the corneal surface, while LL tilted in and thinned. A scaled model diagram was created and revealed an over-blink of the UL over the LL (>0.7mm) and a height offset of the posterior lid margin of >0.7mm. In vitro: the LL TM fused with the UL TM even before full lid touch due to capillary bridge building. CONCLUSIONS: The central UL overlaps the central LL during spontaneous blinking. This provides the appearance of complete closure. The space that results from the lack of lid margin apposition influences the fusion of the upper and lower TM and ultimately tear film mixing.

A novel lid seal evaluation: the Korb-Blackie light test.

PURPOSE: To develop a clinical method to qualitatively evaluate whether a compromised moisture seal is possible even when the lids are apparently closed and to compare these findings with symptoms of ocular discomfort on awakening. METHODS: Patients (n=116) were fully consented and enrolled. The Korb-Blackie lid-light evaluation was performed by placing a transilluminator against the relaxed, closed, outer upper eyelids of semi-reclined patients. The amount of visible light emanating from the lid area between the lashes was quantified on a scale of 0 to 3, where 0=no light, 1=minimal, 2=moderate, and 3=severe for temporal, central, and nasal sections of the eyelids. Eye discomfort on awakening was quantified on a scale of 0 to 2 (0=no discomfort, 1=mild, and 2=significant discomfort). RESULTS: Data are presented for right eyes only. The mean age of the patients was 52.6±16.8 years. The central lid section had a positive lid-light score (54.3%), significantly more frequently than the nasal (37.9%) or temporal (21.6%) lid sections (P<0.0001). Patients with a positive lid-light evaluation were significantly more likely to have symptoms of discomfort on awakening (P<0.0001). CONCLUSION: Light emanating from between "closed" lids during the Korb-Blackie lid-light evaluation is associated with symptoms of ocular discomfort on awakening. These symptoms of discomfort may be linked to the inability of the lids to achieve an adequate seal to prevent subtle ocular surface desiccation during sleeping.

Debridement-scaling: a new procedure that increases Meibomian gland function and reduces dry eye symptoms.

PURPOSE: To evaluate whether a new in-office procedure, the mechanical debridement-scaling of the line of Marx (LOM) and keratinized lid margin, improves meibomian gland (MG) function and reduces dry eye symptoms. METHODS: Twenty-eight patients symptomatic for and diagnosed with evaporative dry eye (16 test patients and 12 controls), who also evidenced anteroplacement and a thickened LOM, were enrolled and consented. SYMPTOMS were evaluated with the Standard Patient Evaluation of Eye Dryness questionnaire. The MG function was evaluated with the standardized MG function evaluator. The LOM was stained with lissamine green (Odyssey Medical, TN) for evaluation. For the test group only, the stained LOM and the entire width of the keratinized lower lid margin were debrided-scaled using a stainless steel, foreign body, golf club spud (Hilco Wilson Ophthalmics, Plainville, MA). All the patients were monitored for change in symptoms and MG function approximately 1 month later. RESULTS: The mean ages of the patients were 55.9 ± 15.0 years (test) versus 53.7 ± 15.3 years (control). There was a significant improvement in the symptoms and MG function 1 month post-debridement-scaling in the test group. The controls evidenced no significant change in either parameter. SYMPTOMS: baseline mean pre-debridement-scaling: 13.4 ± 4.6 (test) versus 13.9 ± 5.5 (control); 1 month post-debridement-scaling: 10.5 ± 3.8 (test, population level statistic < 0.0001) versus 14.3 ± 7.5 (control, population level statistic > 0.05). Number of functional MGs: baseline mean pre-debridement-scaling: 2.6 ± 1.3 (test) versus 2.7 ± 1.5 (control); 1 month post-debridement-scaling: 3.8 ± 1.4 (test, P = 0.0007) versus 2.4 ± 1.1 (control, P > 0.05). Only data for the right eye are reported. CONCLUSIONS: The debridement-scaling of the LOM and lower lid margin provides statistically significant symptom relief and improvement in the MG function. The novel procedure should be considered in the management of MGD and evaporative dry eye.

Psychometric properties and validation of the Standard Patient Evaluation of Eye Dryness questionnaire.

PURPOSE: To characterize the psychometric properties of the standard patient evaluation of eye dryness (SPEED) questionnaire and to validate and compare its performance with 4 existing dry eye questionnaires. METHODS: A total of 50 subjects (40 female and 10 male) were enrolled; of these, 30 were symptomatic and 20 asymptomatic, as determined using the ocular surface disease index (OSDI). This study consisted of 2 visits in which all subjects completed 5 different dry eye questionnaires (SPEED, OSDI, dry eye questionnaire, McMonnies dry eye questionnaire, and subjective evaluation of symptom of dryness) in random order at each visit. Clinical measurements were obtained on the first visit. Repeatability was determined using concordance correlation coefficient; dimensionality was determined using principal component, factor, and Rasch analyses; and validity was determined by comparing SPEED scores with dry eye diagnosis based on OSDI (primarily using receiver-operator curve analysis). RESULTS: The SPEED questionnaire data were found to be unidimensional and repeatable. Three principal components (dryness, burning, and soreness/fatigue) were identified and SPEED between visit concordance correlation coefficient was 0.923 (95% confidence interval, 0.868-0.955). The area under the receiver-operator curves was 0.928. The only clinical measures that correlated "well" with SPEED questionnaire scores were corneal staining (P < 0.05), meibomian gland score (P < 0.05), and meibomian glands yielding liquid secretion score (P < 0.05). CONCLUSIONS: The SPEED questionnaire was shown to be a repeatable and valid instrument for measurement of dry eye symptoms. The SPEED score also correlated significantly with ocular surface staining and clinical measures of meibomian gland function.

Using goggles to increase periocular humidity and reduce dry eye symptoms.

OBJECTIVE: To investigate the use of goggles to increase periocular humidity and reduce dry eye symptoms. METHODS: Noncontact lens wearing patients, previously diagnosed with and symptomatic for dry eye, were recruited. All patients, test (n = 100) and control (n = 25) patients, were required to fill out a simple questionnaire to assess their ocular comfort at three time points during the study: immediately before wearing goggles, after 20 minutes of continuous goggle wear, and 15 minutes after the goggles were removed. The test group consisted of 100 patients who wore swim goggles. The randomly selected control group consisted of 25 patients who wore goggles with the central lens cut out. RESULTS: Ninety-nine percent of the patients in the test group reported a decrease in their symptoms after the goggles had been worn for 20 minutes. After the goggles had been removed for 15 minutes, the symptoms returned in 88% of the test patients. In the control group, only 24% experienced an improvement in symptoms during goggle wear; 76% experienced no improvement. CONCLUSIONS: Increasing the periocular humidity has a significant positive impact on ocular comfort in patients with dry eye. This effect is transient. However, the significance of the improvement is such that the use of goggles should be revisited to help patients suffering from chronic discomfort and other dry eye sequelae. Furthermore, the response of an individual patient to short-term goggle wear may help streamline treatment options for both physicians and patients.

Warm compresses and the risks of elevated corneal temperature with massage.

PURPOSES: To quantify the changes in corneal temperature resulting from intensive warm compress (WC) application with minimal pressure and to review the significance of these changes within the context of the peer-reviewed literature. METHODS: WC were applied intensively and unilaterally at 45 ± 0.5°C for 30 minutes with the contralateral eye serving as a control. Outer upper eyelid and central corneal surface temperatures were measured using an Infrared pyrometer at baseline. The WC were removed for repeat measurements of the outer upper eyelid surface and central corneal temperatures every 2 minutes and replaced with a new WC heated to 45 ± 0.5°C. Lid and corneal temperatures were monitored for 10 minutes after the final WC application. RESULTS: The mean age of the subjects was 37.1 ± 15.0 years (n = 12). The mean maximum outer upper lid temperature of 42.2 ± 1.3°C was reached after 6 minutes. The mean maximum corneal temperature of 39.4 ± 0.7°C was reached after 8 minutes of heating. The control eye showed no significant change in temperature from baseline throughout the experimental period. CONCLUSIONS: These data show that WC use for lid warming, even when only minimal contact pressure is applied, also transfers significant heat to the cornea. Corneal temperatures reach peak temperature after about 8 minutes of WC application. Recent reports discussing the increased potential for transient and long-term corneal molding subsequent to the heat and pressure of WC application are briefly reviewed.

Case report: a successful LipiFlow treatment of a single case of meibomian gland dysfunction and dropout.

OBJECTIVE: The aim of this study was to investigate whether a single case of meibomian gland dysfunction (MGD), with significant MG dropout resulting in evaporative dry eye, could be effectively treated with the LipiFlow (a new Food and Drug Administration-approved thermodynamic pulsatile treatment). MATERIALS AND METHODS: A 39-year-old white woman experienced severe dry eye symptoms because of MGD with considerable MG dropout resulting in evaporative dry eye. Standardized diagnostic MG expression and meibography led to the tentative diagnosis of nonobvious MGD (only 1 functional MG on each lower lid) and MG dropout (∼50% of the lower lid MGs were missing with the remaining MGs being severely truncated). The patient underwent a single 12-min LipiFlow treatment per eye and returned for follow-up at 1 and 7 months posttreatment. RESULTS: The LipiFlow treatment increased the number of functional lower lid MGs from 1 to 5 glands OD and 1 to 7 glands OS at 1 month with slight regression at 7 months (4 OD and 4 OS); increased fluorescein break-up time from 4 to 7 sec OD and 4 to 9 sec OS at both 1 and 7 months; and decreased symptom scores by approximately 50% at 1 month and approximately 75% at 7 months. CONCLUSIONS: These results demonstrate the effectiveness of the LipiFlow in restoring MG function and improving ocular comfort even in this particular case of significant MG dropout and MG truncation.

Evidence suggesting that the keratinized portions of the upper and lower lid margins do not make complete contact during deliberate blinking.

PURPOSE: To investigate whether the keratinized portions of the upper and lower eyelid margins make complete contact during deliberate blinking. METHODS: Ten asymptomatic subjects (21.7 ± 1.5 years) with healthy eyelids were enrolled. A 0.1-µL drop of unpreserved 2% fluorescein placed in the temporal (T) third of the keratinized lower lid margin was observed for 10 deliberate blinks, under 16× magnification. If 10 complete blinks did not alter the drop, the subject squeezed their lids shut. The number of lid squeezes to alter the drop appearance was recorded and repeated for the central (C) and nasal (N) sections. Meibomian gland (MG) functionality was assessed with standardized diagnostic expression. Liquid fluorescein was used to assess the proximity of the line of Marx (LOM) to the lower lid MG orifices. RESULTS: In all cases, 10 complete deliberate blinks did not alter the drop. The mean numbers of lid squeezes to alter the drop was: T = 1.5 ± 1.3, C = 1.9 ± 1.8, and N = 1.2 ± 0.8. The mean number of functional MGs per lid section was as follows: T = 0.8 ± 2.2, C = 4.3 ± 2.3, and N = 4.4 ± 0.8. The LOM relative to the MG orifices was as follows-T: LOM in 30% of eyes was posterior to the MG orifices and in 70% of eyes was mixed (a combination of the LOM posterior, touching, bisecting, or anterior to the MG orifices); C: 70% posterior, 30% mixed; and N: 90% posterior, 10% mixed. CONCLUSIONS: Counterintuitively, the keratinized portions of the upper and lower eyelid margins frequently do not make full contact during what appears to be complete blinking.

The lid wiper contains goblet cells and goblet cell crypts for ocular surface lubrication during the blink.

PURPOSE: The conjunctival side of the upper and lower inner eyelid borders, termed the lid wiper, has a thickened epithelial lip for apposition to the globe, assumed to distribute the preocular tear film. The human lid wiper structure and its goblet cells are investigated. METHODS: Conjunctival whole mounts, including lid margins from 17 eyes of human body donors, were investigated by routine histology and semithin plastic sections, using histology, histochemistry, and immunohistochemistry. RESULTS: In routine histology, the conjunctival lid wiper epithelium regularly showed goblet cells, single and in clusters, at the luminal surface and also deep within the epithelium without apparent surface contact. Semithin sections revealed that the deep goblet cells were often connected to cryptal epithelial infoldings that opened to the surface, hence making their mucins available at the surface. The goblet cells produced mucins of neutral (periodic acid-Schiff) and acidic (Alcian blue) type and stained positive for the gel-forming mucin MUC5AC. Surprisingly, MUC5AC-negative goblet cells were also observed in the lid wiper. CONCLUSIONS: Contrary to conventional assumptions, the lid wiper is part of the conjunctiva. It contains previously undescribed goblet cell crypts deep in the epithelium, suitable as an internal lubrication system for reduction of friction between the lid margin and the globe. This provides the first evidence of the morphological basis for the hydrodynamic type of lubrication and a more conclusive understanding of lid-margin lubrication and tear film distribution. It is another strong indication that the lid wiper is that area in apposition with the globe for distributing the thin preocular tear film during the blink.